Search results for: transition pathways

Authors: Aico Nogueira

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This paper examines the interinstitutional dialogues within the Brazilian federal structures, which comprises federal, state and local levels, around the themes of new approaches and interventions aimed to promote sustainable rural development, particularly rural development as part of a territorial approach. The work seeks to understand to what extent the various levels of the state interact with these strategies, particularly with the locally constituted powers, focusing on the importance of the transition of traditional agriculture methods to more sustainable agroecological systems and its effects on food security and sustainable rural development. The research analyses as case studies the Sustainable Rural Territories Development Program (PRONAT) of the Ministry of Agrarian Development at the federal level, as well as the State of São Paulo and the Vale do Ribeira Territory, an area characterized by environmental and social vulnerability, restrictive environmental laws and attempts to promote sustainable development. In order to examine how the interrelationships between different levels of governance and civil society, in addition to the neo-institutionalist polity centered literature, the research uses an adaptation of the concept of arena in Ostrom and Hannigan, produced at different scales of decision-making processes, as well as the multilevel governance literature. Document analysis, interviews, focus groups and direct observation techniques are also used. The main findings of this study are that how different levels of governance understand and organize themselves for this work and have a direct impact on the actions taken. Consequently, programs formulated for this purpose are not associated with the creation of institutions capable of breaking with a traditional sectoral view that has historically prevailed in policymaking. And the transition from traditional agriculture to agroecological production systems is hampered by a sectorial foundation, based on large-scale production and the strengthening of the traditional country's land concentration model.

Keywords: agroecology, food security, inter-institutional dialogue, rural poverty, sustainable rural development, territorial development

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Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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Authors: Neha Bhadauria, Indu Gaur, Shilpi Shilpi, Susmita Goswami, Prabir K. Paul

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The aerial surface of plants colonized by Human Enteric Pathogens ()has been implicated in outbreaks of enteric diseases in humans. Practice of organic farming primarily using animal dung as manure and sewage water for irrigation are the most significant source of enteric pathogens on the surface of leaves, fruits and vegetables. The present work aims to have an insight into the molecular mechanism of interaction of Human Enteric Pathogens or their metabolites with cell wall receptors in plants. Tomato plants grown under aseptic conditions at 12 hours L/D photoperiod, 25±1°C and 75% RH were inoculated individually with S. fonticola and K. pneumonia. The leaves from treated plants were sampled after 24 and 48 hours of incubation. The cell wall and cytoplasmic proteins were extracted and isocratically separated on 1D SDS-PAGE. The sampled leaves were also subjected to formaldehyde treatment prior to isolation of cytoplasmic proteins to study protein-protein interactions induced by Human Enteric Pathogens. Protein bands extracted from the gel were subjected to MALDI-TOF-TOF MS analysis. The foremost interaction of Human Enteric Pathogens on the plant surface was found to be cell wall bound receptors which possibly set ups a wave a critical protein-protein interaction in cytoplasm. The study revealed the expression and suppression of specific cytoplasmic and cell wall-bound proteins, some of them being important components of signaling pathways. The results also demonstrated HEP induced rearrangement of signaling pathways which possibly are crucial for adaptation of these pathogens to plant surface. At the end of the study, it can be concluded that controlling the over-expression or suppression of these specific proteins rearrange the signaling pathway thus reduces the outbreaks of food-borne illness.

Keywords: cytoplasmic protein, cell wall-bound protein, Human Enteric Pathogen (HEP), protein-protein interaction

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Authors: Atena Sadat Hosseini, Mohammadhossein Habibi

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Acute myeloid leukemia (AML) is the most typically diagnosed leukemia. In older adults, AML imposes a dismal outcome. AML originates with a dominant mutation, then adds collaborative, transformative mutations leading to myeloid transformation and clinical/biological heterogeneity. Several chemotherapeutic drugs are used for this cancer. These drugs are naturally associated with several side effects, and finding a more accurate molecular mechanism of these drugs can have a significant impact on the selection and better candidate of drugs for treatment. In this study, we evaluated bortezomibin myeloma cells using bioinformatics analysis and evaluation of RNA-Seq data. Then investigated the molecular pathways proteins- proteins interactions associated with this chemotherapy drug. A total of 658upregulated genes and 548 downregulated genes were sorted.AUF1 (hnRNP D0) binds and destabilizes mRNA, degradation of GLI2 by the proteasome, the role of GTSE1 in G2/M progression after G2 checkpoint, TCF dependent signaling in response to WNT demonstrated in upregulated genes. Besides insulin resistance, AKT phosphorylates targets in the nucleus, cytosine methylation, Longevity regulating pathway, and Signal Transduction of S1P Receptor were related to low expression genes. With respect to this results, HIST2H2AA3, RP11-96O20.4, ZED9, PRDX1, and DOK2, according to node degrees and betweenness elements candidates from upregulated genes. in the opposite side, PYURF, NRSN1, FGF23, UPK3BL, and STAG3 were a prominent role in downregulated genes. Sum up, Using in silico analysis in the present study, we conducted a precise study ofbortezomib molecular mechanisms in myeloma cells. so that we could take further evaluation to discovermolecular cancer therapy. Naturally, more additional experimental and clinical procedures are needed in this survey.

Keywords: myeloma cells, acute myeloid leukemia, bioinformatics analysis, bortezomib

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Authors: Panagiotis Lemonakis, Theodoros Αlimonakis, George Kaliabetsos, Nikos Eliou

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It is very well known that certain vertical and longitudinal slopes have to be assured in order to achieve adequate rainwater runoff from the pavement. The selection of longitudinal slopes, between the turning points of the vertical curves that meet the afore-mentioned requirement does not ensure adequate drainage because the same condition must also be applied at the transition curves. In this way none of the pavement edges’ slopes (as well as any other spot that lie on the pavement) will be opposite to the longitudinal slope of the rotation axis. Horizontal and vertical alignment must be properly combined in order to form a road which resultant slope does not take small values and hence, checks must be performed in every cross section and every chainage of the road. The present research investigates the rain water runoff from the road surface in order to identify the conditions under which, areas of inadequate drainage are being created, to analyze the rainwater behavior in such areas, to provide design examples of good and bad drainage zones and to track down certain motorcycle types which might encounter hazardous situations due to the presence of water film between the pavement and both of their tires resulting loss of traction. Moreover, it investigates the combination of longitudinal and cross slope values in critical pavement areas. It should be pointed out that the drainage gradient is analytically calculated for the whole road width and not just for an oblique slope per chainage (combination of longitudinal grade and cross slope). Lastly, various combinations of horizontal and vertical design are presented, indicating the crucial zones of bad pavement drainage. The key conclusion of the study is that any type of motorcycle will travel for some time inside the area of improper runoff for a certain time frame which depends on the speed and the trajectory that the rider chooses along the transition curve. Taking into account that on this section the rider will have to lean his motorcycle and hence reduce the contact area of his tire with the pavement it is apparent that any variations on the friction value due to the presence of a water film may lead to serious problems regarding his safety. The water runoff from the road pavement is improved when between reverse longitudinal slopes, crest instead of sag curve is chosen and particularly when its edges coincide with the edges of the horizontal curve. Lastly, the results of the investigation have shown that the variation of the longitudinal slope involves the vertical shift of the center of the poor water runoff area. The magnitude of this area increases as the length of the transition curve increases.

Keywords: drainage, motorcycle safety, superelevation, transition curves, vertical grade

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Authors: Josef Fládr, Jiří Němeček, Veronika Koudelková, Petr Bílý

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Mechanical parameters of cementitious composites differ quite significantly based on the composition of cement matrix. They are also influenced by mixing times and procedure. The research presented in this paper was aimed at identification of differences in microstructure of normal strength (NSC) and differently mixed high strength (HSC) cementitious composites. Scanning electron microscopy (SEM) investigation together with energy dispersive X-ray spectroscopy (EDX) phase analysis of NSC and HSC samples was conducted. Evaluation of interfacial transition zone (ITZ) between the aggregate and cement matrix was performed. Volume share, thickness, porosity and composition of ITZ were studied. In case of HSC, samples obtained by several different mixing procedures were compared in order to find the most suitable procedure. In case of NSC, ITZ was identified around 40-50% of aggregate grains and its thickness typically ranged between 10 and 40 µm. Higher porosity and lower share of clinker was observed in this area as a result of increased water-to-cement ratio (w/c) and the lack of fine particles improving the grading curve of the aggregate. Typical ITZ with lower content of Ca was observed only in one HSC sample, where it was developed around less than 15% of aggregate grains. The typical thickness of ITZ in this sample was similar to ITZ in NSC (between 5 and 40 µm). In the remaining four HSC samples, no ITZ was observed. In general, the share of ITZ in HSC samples was found to be significantly smaller than in NSC samples. As ITZ is the weakest part of the material, this result explains to large extent the improved mechanical properties of HSC compared to NSC. Based on the comparison of characteristics of ITZ in HSC samples prepared by different mixing procedures, the most suitable mixing procedure from the point of view of properties of ITZ was identified.

Keywords: electron diffraction spectroscopy, high strength concrete, interfacial transition zone, normal strength concrete, scanning electron microscopy

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Authors: Sima Saadi, Carolyn Johns

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The concept of a "Smart Water City" is emerging as a framework to address critical urban water challenges, integrating technology, data, and sustainable management practices to enhance water quality, conservation, and accessibility. This paper explores the definition of a Smart Water City, examines the pressing need for such cities in Canada, and proposes policy pathways for their development. Smart Water Cities utilize advanced monitoring systems, data analytics, and integrated water resources management to optimize water usage, anticipate and mitigate environmental impacts, and engage citizens in sustainable practices. Global examples from regions such as Europe, Asia, and Australia illustrate how Smart Water City models can transform urban water systems by enhancing resilience, improving resource efficiency, and driving economic development through job creation in environmental technology sectors. For Canada, adopting Smart Water City principles could address pressing challenges, including climate-induced water stress, aging infrastructure, and the need for equitable water access across diverse urban and rural communities. Building on Canada's existing water policies and technological expertise, it propose strategic investments in digital water infrastructure, data-driven governance, and community partnerships. Through case studies, this paper offers insights into how Canadian cities could benefit from cross-sector collaboration, policy development, and funding for smart water technology. By aligning national policy with smart urban water solutions, Canada has the potential to lead globally in sustainable water management, ensuring long-term water security and environmental stewardship for its cities and communities.

Keywords: smart water city, urban water resilience, water management technology, sustainable water infrastructure, canada water policy, smart city initiatives

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Authors: Ozgu Turgut

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Water scarcity is a problem for many regions which requires immediate action, and solutions cannot be postponed for a long time. It is known that farming consumes a significant portion of usable water. Although in recent years, the efforts to make the transition to dripping or spring watering systems instead of using surface watering started to pay off. It is also known that this transition is not necessarily translated into an increase in the capacity dedicated to other water consumption channels such as city water or power usage. In order to control and allocate the water resource more purposefully, new watering systems have to be used with monitoring abilities that can limit the usage capacity for each farm. In this study, a decision support model which relies on a bi-objective stochastic linear optimization is proposed, which takes crop yield and price volatility into account. The model generates annual planting plans as well as water usage limits for each farmer in the region while taking the total value (i.e., profit) of the overall harvest. The mathematical model is solved using the L-shaped method optimally. The decision support model can be especially useful for regional administrations to plan next year's planting and water incomes and expenses. That is why not only a single optimum but also a set of representative solutions from the Pareto set is generated with the proposed approach.

Keywords: decision support, farming, water, tactical planning, optimization, stochastic, pareto

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Authors: Yuzhen Hu, Sirui Wang

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As a training base for intellectual talents, universities have a large number of students. Teaching is a primary activity in universities, and during the teaching process, a large number of people gather both inside and outside the teaching buildings, posing a strong risk of close contact. The class schedule is the fundamental basis for teaching activities in universities and plays a crucial role in the management of teaching order. Different class schedules can lead to varying degrees of indoor gatherings and trajectories of class attendees. In recent years, highly contagious diseases have frequently occurred worldwide, and how to reduce the risk of infection has always been a hot issue related to public safety. "Reducing gatherings" is one of the core measures in epidemic prevention and control, and it can be controlled through scientific scheduling in specific environments. Therefore, the scientific prevention and control goal can be achieved by considering the reduction of the risk of excessive gathering of people during the course schedule arrangement. Firstly, we address the issue of personnel gathering in various pathways on campus, with the goal of minimizing congestion and maximizing teaching effectiveness, establishing a nonlinear mathematical model. Next, we design an improved genetic algorithm, incorporating real-time evacuation operations based on tracking search and multidimensional positive gradient cross-mutation operations, considering the characteristics of outdoor crowd evacuation. Finally, we apply undergraduate course data from a university in Harbin to conduct a case study. It compares and analyzes the effects of algorithm improvement and optimization of gathering situations and explores the impact of path blocking on the degree of gathering of individuals on other pathways.

Keywords: the university timetabling problem, risk prevention, genetic algorithm, risk control

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Authors: Ankan Roy, Niharika, Samir Kumar Patra

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Anomalous nexus of complex topological assemblies and spatiotemporal epigenetic choreography at chromosomal territory may forms the most sophisticated regulatory layer of gene expression in cancer. Colon cancer is one of the leading malignant neoplasms of the lower gastrointestinal tract worldwide. There is still a paucity of information about the complex molecular mechanisms of colonic cancerogenesis. Bioinformatics prediction and analysis helps to identify essential genes and significant pathways for monitoring and conquering this deadly disease. The present study investigates and explores potential hub genes as biomarkers and effective therapeutic targets for colon cancer treatment. Colon cancer patient sample containing gene expression profile datasets, such as GSE44076, GSE20916, and GSE37364 were downloaded from Gene Expression Omnibus (GEO) database and thoroughly screened using the GEO2R tool and Funrich software to find out common 2 differentially expressed genes (DEGs). Other approaches, including Gene Ontology (GO) and KEGG pathway analysis, Protein-Protein Interaction (PPI) network construction and hub gene investigation, Overall Survival (OS) analysis, gene correlation analysis, methylation pattern analysis, and hub gene-Transcription factors regulatory network construction, were performed and validated using various bioinformatics tool. Initially, we identified 166 DEGs, including 68 up-regulated and 98 down-regulated genes. Up-regulated genes are mainly associated with the Cytokine-cytokine receptor interaction, IL17 signaling pathway, ECM-receptor interaction, Focal adhesion and PI3K-Akt pathway. Downregulated genes are enriched in metabolic pathways, retinol metabolism, Steroid hormone biosynthesis, and bile secretion. From the protein-protein interaction network, thirty hub genes with high connectivity are selected using the MCODE and cytoHubba plugin. Survival analysis, expression validation, correlation analysis, and methylation pattern analysis were further verified using TCGA data. Finally, we predicted COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as potential master regulators in colonic cancerogenesis. Moreover, our experimental data highlights that disruption of lipid raft and RAS/MAPK signaling cascade affects this gene hub at mRNA level. We identified COL1A1, COL1A2, COL4A1, SPP1, SPARC, and THBS2 as determinant hub genes in colon cancer progression. They can be considered as biomarkers for diagnosis and promising therapeutic targets in colon cancer treatment. Additionally, our experimental data advertise that signaling pathway act as connecting link between membrane hub and gene hub.

Keywords: hub genes, colon cancer, DNA methylation, epigenetic engineering, bioinformatic predictions

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Authors: Lateefat Amao, Misagh Faezipour

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Implementing electronic health records (EHR) in healthcare is a pivotal transition aimed at digitizing and optimizing patient health information management. The expectations associated with this transition are high, even towards other health information systems (HIS) and health technology. This multifaceted process involves careful planning and execution to improve the quality and efficiency of patient care, especially as healthcare technology is a sensitive niche. Key considerations include a thorough needs assessment, judicious vendor selection, robust infrastructure development, and training and adaptation of healthcare professionals. Comprehensive training programs, data migration from legacy systems and models, interoperability, as well as security and regulatory compliance are imperative for healthcare staff to navigate EHR systems adeptly. The purpose of this work is to offer a comprehensive review of the literature on EHR implementation. It explores the impact of this health technology on health practices, highlights challenges and barriers to its successful utility, and offers practical strategies that can impact its success in healthcare. This paper provides a thorough review of studies on the adoption of EHRs, emphasizing the wide range of experiences and results connected to EHR use in the medical field, especially across different types of healthcare organizations.

Keywords: healthcare, electronic health records, EHR implementation, patient care, interoperability

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Authors: Chao Wu

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Thioredoxin reductase 2 is a mitochondrial enzyme that belongs to the cellular defense against oxidative stress. We deleted mitochondrial Txnrd2 in a KrasG12D-driven pancreatic tumor model. Despite an initial increase in precursor lesions, tumor incidence decreased significantly. We isolated cancer cell lines from these genetically engineered mice and observed an impaired proliferation and colony formation. Reactive Oxygen Species, as determined by DCF fluorescence, were increased. We detected a higher mitochondrial copy number in Txnrd2-deficient cells (KTP). However, measurement of mitochondrial bioenergetics showed no impairment of mitochondrial function and comparable O₂-consumption and extracellular acidification rates. In addition, the mitochondrial complex composition was affected in Txnrd2 deleted cell lines. To gain better insight into the role of Txnrd2, we deleted Txnrd2 in clones from parental KrasG12D cell lines using Crispr/Cas9 technology. The deletion was confirmed by western blot and activity assay. Interestingly, and in line with previous RNA expression analysis, we saw changes in EMT markers in Txnrd2 deleted cell lines and control cell lines. This might help us explain the reduced tumor incidence in KrasG12D; Txnrd2∆panc mice.

Keywords: PDAC, TXNRD2, epithelial-to-mesenchymal-transition, ROS

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Authors: Sunil Kumar, Sandip Dhole, Deepak Salunke, Chung-ming Sun

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Heterocycles bearing nitrogen, oxygen, and selenium are present in innumerable biologically active compounds. For instance, coumarin containing dicoumarol acts as naturally occurring anticoagulant. 2-Acylamido selenazole works as Store-Operated Calcium (SOC) channel regulator. Therefore, due to biologically significance of selenazole and coumarin and our quest to develop efficient methodologies for the synthesis of complex heterocycles, the trisubstituted angular isocoumarinoselenazole synthesis was proposed and achieved by starting from nitrobenzoic acid derivative, available commercially. Synthetic procedure involves three steps: i) the construction of 2-aminobenzoselenazoles, ii) their regioselective N-alkylation at position-2 and iii) alkyne insertion via Ru catalyzed C-H activation. Transition metal free synthesis of benzoselenazoles was successfully brought about by the addition/elimination reaction via intramolecular C-Se bond formation. In the next step, N-alkylation of selenazole furnished two regioisomers. Both the isomers exhibited different reactivity towards [4+2] alkyne annulation reaction. The fusion of α-pyrone ring on the benzo[1,3-d]selenazole skeleton was achieved via Ru(II)-catalyzed C-H activation and alkyne insertion. As evident from mechanism, the selenazole 'N' plays an important role for the experiential selectivity.

Keywords: alkylation, alkyne insertion, coumarin, selenazole

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Authors: Zeynep Yazicioglu

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Project development is a complex process where many stakeholders work together. Employers and main contractors are the base stakeholders, whereas designers, engineers, sub-contractors, suppliers, supervisors, and consultants are other stakeholders. A combination of the complexity of the building process with a large number of stakeholders often leads to time and cost overruns and irregular resource utilization. Failure to comply with the work schedule and inefficient use of resources in the construction processes indicate that it is necessary to accelerate production and increase productivity. The development of computer software called Building Information Modeling, abbreviated as BIM, is a major technological breakthrough in this area. The use of BIM enables architectural, structural, mechanical, and electrical projects to be drawn in coordination. BIM is a tool that should be considered by every stakeholder with the opportunities it offers, such as minimizing construction errors, reducing construction time, forecasting, and determination of the final construction cost. It is a process spreading over the years, enabling all stakeholders associated with the project and construction to use it. The main goal of this paper is to explore the problems associated with the adoption of BIM in multi-stakeholder projects. The paper is a conceptual study, summarizing the author’s practical experience with design offices and construction firms working with BIM. In the transition period to BIM, three of the challenges will be examined in this paper: 1. The compatibility of supplier companies with BIM, 2. The need for two-dimensional drawings, 3. Contractual issues related to BIM. The paper reviews the literature on BIM usage and reviews the challenges in the transition stage to BIM. Even on an international scale, the supplier that can work in harmony with BIM is not very common, which means that BIM's transition is continuing. In parallel, employers, local approval authorities, and material suppliers still need a 2-D drawing. In the BIM environment, different stakeholders can work on the same project simultaneously, giving rise to design ownership issues. Practical applications and problems encountered are also discussed, providing a number of suggestions for the future.

Keywords: BIM opportunities, collaboration, contract issues about BIM, stakeholders of project

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Authors: S. U. Khan, T. Ayub, N. Shafiq

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The properties of locally produced metakaolin (MK) as cement replacing material and the comparison of reactivity with commercially available micro-silica have been investigated. Compressive strength, splitting tensile strength, and load-deflection behaviour under bending are the properties that have been studied. The amorphous phase of MK with micro-silica was compared through X-ray diffraction (XRD) pattern. Further, interfacial transition zone of concrete with micro-silica and MK was observed through Field Emission Scanning Electron Microscopy (FESEM). Three mixes of concrete were prepared. One of the mix is without cement replacement as control mix, and the remaining two mixes are 10% cement replacement with micro-silica and MK. It has been found that MK, due to its irregular structure and amorphous phase, has high reactivity with portlandite in concrete. The compressive strength at early age is higher with MK as compared to micro-silica. MK concrete showed higher splitting tensile strength and higher load carrying capacity as compared to control and micro-silica concrete at all ages respectively.

Keywords: metakaolin, compressive strength, splitting tensile strength, load deflection, interfacial transition zone

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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: Mohammad Altaf Hossain

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A growing body of literature in urban studies has presented that urban precarity has been a lived experience for low-income groups of people in the cities of the Global South. It does not necessarily mean that cities in the Global North, where advanced capitalist economies exist, avoided the adverse realities of urban precarity. As a multifaceted condition, it creates other associated precariousness in lives -for example, economic deprivation, mental stress, and housing precarity. The interrelations between urbanity and precarity have been ubiquitous regardless of the developed and developing countries. People, mainly manual labourers with low incomes, go through uncertainties in every aspect of life. By analysing qualitative data and embracing structure-agency interaction, this paper intends to present how Bangladeshi migrants experience housing precarity in Dublin. Continued population growth and political economy factors such as labour market inequality, financialisation of the private rental sector, and the impact of cuts to government funding for social housing provision are combined to produce a housing supply crisis, affordability, and access in the city. As a result, low-income people practice informality in securing jobs and housing. The macro-structural components of this analysis include the Irish housing policy, the European labour market, the immigration policy, and the financialised housing market. The micro-structural components of South Asian communities’ experiences include social networks and social class. Access to social networks and practices of informality play a significant role in enabling them to negotiate urban precarity, including housing crises and income insecurity. In some cases, the collective agency of ethnic diaspora communities plays a vital role in negotiating with structural constraints.

Keywords: housing precarity, housing pathways, migration, agency, Dublin

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Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

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Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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Authors: Raheleh Hajilou

Abstract:

In this study, we report the synthesis and characterization of YBa2Cu3O7-δ (YBCO) high-temperature superconductor prepared by solid-state method and doped with Sm in different weight percentages, 0, 0.01, 0.02 and 0.05 wt. The result of X-ray diffraction (XRD) analysis conforms to the formation of an orthorhombic phase of superconductivity in our samples. This is an important finding and indicates that the samples may exhibit superconductivity properties at certain conditions. Our results unequivocally point to a different structural order or disorder in SM/Y samples as compared to Sm based samples. We suggest that different site preferences of oxygen vacancies, predominantly created in CuO2 planes (CuO chains) of Y and Sm-based samples, might be responsible for the observed difference in the behavior. This contention is supported by a host of other considerations and experimental observations. The study investigated the effects of Sm doping on the YBCO system on various properties such as structural, critical temperature (Tc), scanning electron microscope (SEM), irresistibility line(IL), critical current density, jc, and flux line pinning force. It Seems the sample x=0.05 undergoes an insulator transition, which suppresses its superconducting transition temperature (Tc). Additionally, magnetization was measured as a function of temperature (M-T) and magnetic loops (M-H) at constant temperatures of 10. 20, 30, 40, 50 and 60K up to 10KG.

Keywords: high-Tc superconductors, Scanning electron microscopy, X-ray scattering, Irreversibility line

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Authors: Mohd Mudasir Shafi, Zafrul Hasan, Talat Saleem

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Information and communication Technology (ICT) services have been defined as a route to good governance. Introduction of ICT into Governance has given rise to the idea of e-governance which helps in enhancing transparency, generating accountability and responsiveness in the system in order to provide faster and quality service to the citizen. Advancement in ICT has provided governments all over the world to speed up the delivery of information and services to citizens and businesses and increase their participation in governance. There has been varying degree of success over the past decade into providing services to the citizens using internet and different web services. These e-government initiatives have been extensively researched. Our research is aimed at the transition from electronic government to mobile government (m-government) initiatives implementing the mobile services and concerned to understand the major factors which will aid to adoption and distribution of these services. There must be some amount of research done in the integration process between e-government and m-government. There must also be enough amount of investigation done all the factors that could affect the transition process. Such factors differ between different places and the advancement in information and technology available there. In this paper, we have discussed why mobile communication system can be used for effective e-governance and the areas where m-governance can be implemented. The paper will examine some of the reasons as well as the main opportunities for improving effective governance through mobile phones.

Keywords: e-governance, mobile phones, information technology, m-government

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Authors: Matúš Mihalik, Martin Vavra, Kornel Csach, Marián Mihalik

Abstract:

GdMnO₃ belongs to orthorhombically distorted, GdFeO₃-type family of perovskite compounds. These compounds are naturally vacant and the amount of vacancies depend on the sample preparation conditions. Our GdMnO₃ samples were prepared by float zone method and the vacancies were controlled using an air, Ar and O₂ preparation atmosphere. The highest amount of vacancies was found for sample prepared in Ar atmosphere, while the sample prepared in O₂ was observed to be almost vacancy-free. The magnetic measurements indicate that the preparation atmosphere has no impact on Néel temperature (TN ~ 42 K), however, it has strong impact on the incommensurate antiferromagnetic (IC) to canted A-type weak ferromagnetic (AWF) phase transition at T1: T1 = 23.4 K; 18 K and 6.7 K for samples prepared in Ar; air and O₂ atmosphere; respectively. The hysteresis loop measured at 2 K has a butterfly-type shape with the remnant magnetization (Mr) of 0.6 µB/f.u. for Ar and air sample, while Mr = 0.3 µB/f.u. for O₂ sample. The shape of the hysteresis loop depends on the preparation atmosphere in magnetic fields up to 1.5 T, but is independent for higher magnetic fields. The coercive field of less than 0.06 T and the maximum magnetic moment of 6 µB/f.u. at magnetic field µ0H = 7 T do not depend on the preparation atmosphere. All these findings indicate that only AWF phase of GdMnO₃ compound is directly affected by the vacancies in the system, while IC phase and the field induced ferroelectric phase are not affected.

Keywords: magnetism, perovskites, sample preparation, magnetic phase transition

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Authors: J. Belovickis, V. Samulionis, J. Banys, M. V. Silibin, A. V. Solnyshkin, A. V. Sysa

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Ferroelectric polymers exhibit good flexibility, processability and low cost of production. Doping of ferroelectric polymers with nanofillers may modify its dielectric, elastic or piezoelectric properties. Carbon nanotubes are one of the ingredients that can improve the mechanical properties of polymer based composites. In this work, we report on both the ultrasonic and the dielectric properties of the copolymer polyvinylidene fluoride/tetrafluoroethylene (P(VDF-TrFE)) of the composition 70/30 mol% with various concentrations of carbon nanotubes (CNT). Experimental study of ultrasonic wave attenuation and velocity in these composites has been performed over wide temperature range (100 K – 410 K) using an ultrasonic automatic pulse-echo tecnique. The temperature dependences of ultrasonic velocity and attenuation showed anomalies attributed to the glass transition and paraelectric-ferroelectric phase transition. Our investigations showed mechanical losses to be dependent on the volume fraction of the CNTs within the composites. The existence of broad hysteresis of the ultrasonic wave attenuation and velocity within the nanocomposites is presented between cooling and heating cycles. By the means of dielectric spectroscopy, it is shown that the dielectric properties may be tuned by varying the volume fraction of the CNT fillers.

Keywords: carbon nanotubes, polymer composites, PVDF-TrFE, ultrasonic spectroscopy

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Authors: Huimin Liu, Li Xiang, Yue Liu, Jing Wang

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Background: As one of typical case for the developing countries who are stepping into the aging times globally, more and more older people in China might face the problem of which they could not maintain normal life due to the functional disability. While the government take efforts to build long-term care system and further carry out related policies for the core concept, there is still lack of strong evidence to evaluating the profile of disability states in the elderly population and its transition rate. It has been proved that disability is a dynamic condition of the person rather than irreversible so it means possible to intervene timely on them who might be in a risk of severe disability. Objective: The aim of this study was to depict the picture of the disability transferring status of the older people in China, and then find out individual characteristics that change the state of disability to provide theory basis for disability prevention and early intervention among elderly people. Methods: Data for this study came from the 2011 baseline survey and the 2013 follow-up survey of the China Health and Retirement Longitudinal Study (CHARLS). Normal ADL function, 1~2 ADLs disability,3 or above ADLs disability and death were defined from state 1 to state 4. Multi-state Markov model was applied and the four-state homogeneous model with discrete states and discrete times from two visits follow-up data was constructed to explore factors for various progressive stages. We modeled the effect of explanatory variables on the rates of transition by using a proportional intensities model with covariate, such as gender. Result: In the total sample, state 2 constituent ratio is nearly about 17.0%, while state 3 proportion is blow the former, accounting for 8.5%. Moreover, ADL disability statistics difference is not obvious between two years. About half of the state 2 in 2011 improved to become normal in 2013 even though they get elder. However, state 3 transferred into the proportion of death increased obviously, closed to the proportion back to state 2 or normal functions. From the estimated intensities, we see the older people are eleven times as likely to develop at 1~2 ADLs disability than dying. After disability onset (state 2), progression to state 3 is 30% more likely than recovery. Once in state 3, a mean of 0.76 years is spent before death or recovery. In this model, a typical person in state 2 has a probability of 0.5 of disability-free one year from now while the moderate disabled or above has a probability of 0.14 being dead. Conclusion: On the long-term care cost considerations, preventive programs for delay the disability progression of the elderly could be adopted based on the current disabled state and main factors of each stage. And in general terms, those focusing elderly individuals who are moderate or above disabled should go first.

Keywords: Markov model, elderly people, disability, transition intensity

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Authors: Tomokazu Shirai, Akihiko Kondo

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Technologies of metabolic engineering or synthetic biology are essential for effective microbial bioproduction. It is especially important to develop an in silico tool for designing a metabolic pathway producing an unnatural and valuable chemical such as fossil materials of fuel or plastics. We here demonstrated two in silico tools for designing novel metabolic pathways: BioProV and HyMeP. Furthermore, we succeeded in creating an artificial metabolic pathway by enzyme engineering.

Keywords: bioinformatics, metabolic engineering, synthetic biology, genome scale model

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Authors: M. Sasajima, M. Watanabe, T. Yamaguchi Y. Kurosawa, Y. Koike

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In very narrow pathways, the speed of sound propagation and the phase of sound waves change due to the air viscosity. We have developed a new Finite Element Method (FEM) that includes the effects of air viscosity for modeling a narrow sound pathway. This method is developed as an extension of the existing FEM for porous sound-absorbing materials. The numerical calculation results for several three-dimensional slit models using the proposed FEM are validated against existing calculation methods.

Keywords: simulation, FEM, air viscosity, slit

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Authors: Anton G. Akulichev, Avinash Tiwari, Ben Alcock, Andreas Echtermeyer

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Low temperatures are known to pose a major threat for polymers; many are prone to excessive stiffness or even brittleness. There is a technology gap between the properties of existing elastomeric sealing materials and the properties needed for service in extremely cold regions. Moreover, some aspects of low temperature behaviour of rubber are not thoroughly studied and understood. The paper presents results of laboratory testing of a conventional oilfield HNBR (hydrogenated nitrile butadiene rubber) elastomer at low climatic temperatures above and below its glass transition point, as well as the performance of some filled HNBR formulations. Particular emphasis in the experiments is put on rubber viscoelastic characteristics studied by Dynamic Mechanical Analysis (DMA) and quasi-static mechanical testing results at low temperatures. As demonstrated by the stress relaxation and DMA experiments the transition region near Tg of the studied compound has the most striking features, like rapid stress relaxation, as compared to the glassy and rubbery plateau. In addition the quasi-static experiments show that molecular movement below Tg is not completely frozen, but rather evident and manifested in a certain stress decay as well. The effect of temperature and filler additions on typical mechanical and other properties of the materials is also discussed.

Keywords: characterization, filled elastomers, HNBR, low temperature

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Authors: Afsaneh Mohammadnejad, Marianne Nygaard, Jan Baumbach, Shuxia Li, Weilong Li, Jesper Lund, Jacob v. B. Hjelmborg, Lene Christensen, Qihua Tan

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Cognitive impairment in the elderly is a key issue affecting the quality of life. Despite a strong genetic background in cognition, only a limited number of single nucleotide polymorphisms (SNPs) have been found. These explain a small proportion of the genetic component of cognitive function, thus leaving a large proportion unaccounted for. We hypothesize that one reason for this missing heritability is the misspecified modeling in data analysis concerning phenotype distribution as well as the relationship between SNP dosage and the phenotype of interest. In an attempt to overcome these issues, we introduced a model-free method based on the generalized correlation coefficient (GCC) in a genome-wide association study (GWAS) of cognitive function in twin samples and compared its performance with two popular linear regression models. The GCC-based GWAS identified two genome-wide significant (P-value < 5e-8) SNPs; rs2904650 near ZDHHC2 on chromosome 8 and rs111256489 near CD6 on chromosome 11. The kinship model also detected two genome-wide significant SNPs, rs112169253 on chromosome 4 and rs17417920 on chromosome 7, whereas no genome-wide significant SNPs were found by the linear mixed model (LME). Compared to the linear models, more meaningful biological pathways like GABA receptor activation, ion channel transport, neuroactive ligand-receptor interaction, and the renin-angiotensin system were found to be enriched by SNPs from GCC. The GCC model outperformed the linear regression models by identifying more genome-wide significant genetic variants and more meaningful biological pathways related to cognitive function. Moreover, GCC-based GWAS was robust in handling genetically related twin samples, which is an important feature in handling genetic confounding in association studies.

Keywords: cognition, generalized correlation coefficient, GWAS, twins

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Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

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Authors: Domenico Carmelo Mongelli, Laura Carnieletto, Michele De Carli, Filippo Busato

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Starting from the current context in which the Russian invasion in Ukraine has highlighted Europe's dependence on natural gas imports for heating buildings, this study proposes solutions to resolve this dependency and evaluates related scenarios in the near future. In the first part of this work the methodologies and results of the economic impact are indicated by simulating a massive replacement of boilers powered by fossil fuels with electrically powered hightemperature air-water heat pumps for heating residential buildings in different European climates, without changing the current energy mix. For each individual European region, the costs for the purchase and installation of heat pumps for all residential buildings have been determined. Again for each individual European region, the economic savings during the operation phase that would be obtained in this future scenario of energy transition from fossil fuels to the electrification of domestic heating were calculated. For the European regions for which the economic savings were identified as positive, the payback times of the economic investments were analysed. In the second part of the work, hypothesizing different scenarios for a possible greater use of renewable energy sources and therefore with different possible future scenarios of the energy mix, the methodologies and results of the simulations on the economic analysis and on the environmental analysis are reported which have allowed us to evaluate the future effects of the energy transition from boilers to heat pumps for each European region. In the third part, assuming a rapid short-term diffusion of cooling for European residential buildings, the penetration shares in the cooling market and future projections of energy needs for cooling for each European region have been identified. A database was created where the results of this research relating to 38 European Nations divided into 179 regions were reported. Other previous works on the topics covered were limited to analyzing individual European nations, without ever going into detail about the individual regions within each nation, while the original contribution of the present work lies in the fact that the results achieved allow a specific numerical analysis and punctual for every single European region.

Keywords: buildings, energy, Europe, future

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