Search results for: future spouse
Commenced in January 2007
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Edition: International
Paper Count: 7395

Search results for: future spouse

585 MTT Assay-Guided Isolation of a Cytotoxic Lead from Hedyotis umbellata and Its Mechanism of Action against Non-Small Cell Lung Cancer A549 Cells

Authors: Kirti Hira, A. Sajeli Begum, S. Mahibalan, Poorna Chandra Rao

Abstract:

Introduction: Cancer is one of the leading causes of death worldwide. Although existing therapy effectively kills cancer cells, they do affect normal growing cells leading to many undesirable side effects. Hence there is need to develop effective as well as safe drug molecules to combat cancer, which is possible through phyto-research. The currently available plant-derived blockbuster drugs are the example for this. In view of this, an investigation was done to identify cytotoxic lead molecules from Hedyotis umbellata (Family Rubiaceae), a widely distributed weed in India. Materials and Methods: The methanolic extract of the whole plant of H. umbellata (MHU), prepared through Soxhlet extraction method was further fractionated with diethyl ether and n-butanol, successively. MHU, ether fraction (EMHU) and butanol fraction (BMHU) were lyophilized and were tested for the cytotoxic effect using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay against non-small cell lung cancer (NSCLC) A549 cell lines. The potentially active EMHU was subjected to chromatographic purification using normal-phase silica columns, in order to isolate the responsible bioactive compounds. The isolated pure compounds were tested for their cytotoxic effect by MTT assay against A549 cells. Compound-3, which was found to be most active, was characterized using IR, 1H- and 13C-NMR and MS analysis. The study was further extended to decipher the mechanism of action of cytotoxicity of compound-3 against A549 cells through various in vitro cellular models. Cell cycle analysis was done using flow cytometry following PI (Propidium Iodide) staining. Protein analysis was done using Western blot technique. Results: Among MHU, EMHU, and BMHU, the non-polar fraction EMHU demonstrated a significant dose-dependent cytotoxic effect with IC50 of 67.7μg/ml. Chromatography of EMHU yielded seven compounds. MTT assay of isolated compounds explored compound-3 as potentially active one, which inhibited the growth of A549 cells with IC50value of 14.2μM. Further, compound-3 was identified as cedrelopsin, a coumarin derivative having molecular weight of 260. Results of in vitro mechanistic studies explained that cedrelopsin induced cell cycle arrest at G2/M phase and down-regulated the expression of G2/M regulatory proteins such as cyclin B1, cdc2, and cdc25C, dose dependently. This is the first report that explores the cytotoxic mechanism of cedrelopsin. Conclusion: Thus a potential small lead molecule, cedrelopsin isolated from H. umbellata, showing antiproliferative effect mediated by G2/M arrest in A549 cells was discovered. The effect of cedrelopsin against other cancer cell lines followed by in vivo studies can be performed in future to develop a new drug candidate.

Keywords: A549, cedrelopsin, G2/M phase, Hedyotis umbellata

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584 European Commission Radioactivity Environmental Monitoring Database REMdb: A Law (Art. 36 Euratom Treaty) Transformed in Environmental Science Opportunities

Authors: M. Marín-Ferrer, M. A. Hernández, T. Tollefsen, S. Vanzo, E. Nweke, P. V. Tognoli, M. De Cort

Abstract:

Under the terms of Article 36 of the Euratom Treaty, European Union Member States (MSs) shall periodically communicate to the European Commission (EC) information on environmental radioactivity levels. Compilations of the information received have been published by the EC as a series of reports beginning in the early 1960s. The environmental radioactivity results received from the MSs have been introduced into the Radioactivity Environmental Monitoring database (REMdb) of the Institute for Transuranium Elements of the EC Joint Research Centre (JRC) sited in Ispra (Italy) as part of its Directorate General for Energy (DG ENER) support programme. The REMdb brings to the scientific community dealing with environmental radioactivity topics endless of research opportunities to exploit the near 200 millions of records received from MSs containing information of radioactivity levels in milk, water, air and mixed diet. The REM action was created shortly after Chernobyl crisis to support the EC in its responsibilities in providing qualified information to the European Parliament and the MSs on the levels of radioactive contamination of the various compartments of the environment (air, water, soil). Hence, the main line of REM’s activities concerns the improvement of procedures for the collection of environmental radioactivity concentrations for routine and emergency conditions, as well as making this information available to the general public. In this way, REM ensures the availability of tools for the inter-communication and access of users from the Member States and the other European countries to this information. Specific attention is given to further integrate the new MSs with the existing information exchange systems and to assist Candidate Countries in fulfilling these obligations in view of their membership of the EU. Article 36 of the EURATOM treaty requires the competent authorities of each MS to provide regularly the environmental radioactivity monitoring data resulting from their Article 35 obligations to the EC in order to keep EC informed on the levels of radioactivity in the environment (air, water, milk and mixed diet) which could affect population. The REMdb has mainly two objectives: to keep a historical record of the radiological accidents for further scientific study, and to collect the environmental radioactivity data gathered through the national environmental monitoring programs of the MSs to prepare the comprehensive annual monitoring reports (MR). The JRC continues his activity of collecting, assembling, analyzing and providing this information to public and MSs even during emergency situations. In addition, there is a growing concern with the general public about the radioactivity levels in the terrestrial and marine environment, as well about the potential risk of future nuclear accidents. To this context, a clear and transparent communication with the public is needed. EURDEP (European Radiological Data Exchange Platform) is both a standard format for radiological data and a network for the exchange of automatic monitoring data. The latest release of the format is version 2.0, which is in use since the beginning of 2002.

Keywords: environmental radioactivity, Euratom, monitoring report, REMdb

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583 Therapeutic Potential of GSTM2-2 C-Terminal Domain and Its Mutants, F157A and Y160A on the Treatment of Cardiac Arrhythmias: Effect on Ca2+ Transients in Neonatal Ventricular Cardiomyocytes

Authors: R. P. Hewawasam, A. F. Dulhunty

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The ryanodine receptor (RyR) is an intracellular ion channel that releases Ca2+ from the sarcoplasmic reticulum and is essential for the excitation-contraction coupling and contraction in striated muscle. Human muscle specific glutathione transferase M2-2 (GSTM2-2) is a highly specific inhibitor of cardiac ryanodine receptor (RyR2) activity. Single channel-lipid bilayer studies and Ca2+ release assays performed using the C-terminal half of the GSTM2-2 and its mutants F157A and Y160A confirmed the ability of the C terminal domain of GSTM2-2 to specifically inhibit the cardiac ryanodine receptor activity. Objective of the present study is to determine the effect of C terminal domain of GSTM2-2 (GSTM2-2C) and the mutants, F157A and Y160A on the Ca2+ transients of neonatal ventricular cardiomyocytes. Primary cardiomyocytes were cultured from neonatal rats. They were treated with GSTM2-2C and the two mutants F157A and Y160A at 15µM and incubated for 2 hours. Then the cells were led with Fluo-4AM, fluorescent Ca2+ indicator, and the field stimulated (1 Hz, 3V and 2ms) cells were excited using the 488 nm argon laser. Contractility of the cells were measured and the Ca2+ transients in the stained cells were imaged using Leica SP5 confocal microscope. Peak amplitude of the Ca2+ transient, rise time and decay time from the peak were measured for each transient. In contrast to GSTM2C which significantly reduced the % shortening (42.8%) in the field stimulated cells, F157A and Y160A failed to reduce the % shortening.Analysis revealed that the average amplitude of the Ca2+ transient was significantly reduced (P<0.001) in cells treated with the wild type GSTM2-2C compared to that of untreated cells. Cells treated with the mutants F157A and Y160A didn’t change the Ca2+ transient significantly compared to the control. A significant increase in the rise time (P< 0.001) and a significant reduction in the decay time (P< 0.001) were observed in cardiomyocytes treated with GSTM2-2C compared to the control but not with F157A and Y160A. These results are consistent with the observation that GSTM2-2C reduced the Ca2+ release from the cardiac SR significantly whereas the mutants, F157A and Y160A didn’t show any effect compared to the control. GSTM2-2C has an isoform-specific effect on the cardiac ryanodine receptor activity and also it inhibits RyR2 channel activity only during diastole. Selective inhibition of RyR2 by GSTM2-2C has significant clinical potential in the treatment of cardiac arrhythmias and heart failure. Since GSTM2-2C-terminal construct has no GST enzyme activity, its introduction to the cardiomyocyte would not exert any unwanted side effects that may alter its enzymatic action. The present study further confirms that GSTM2-2C is capable of decreasing the Ca2+ release from the cardiac SR during diastole. These results raise the future possibility of using GSTM2-2C as a template for therapeutics that can depress RyR2 function when the channel is hyperactive in cardiac arrhythmias and heart failure.

Keywords: arrhythmia, cardiac muscle, cardiac ryanodine receptor, GSTM2-2

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582 The Different Effects of Mindfulness-Based Relapse Prevention Group Therapy on QEEG Measures in Various Severity Substance Use Disorder Involuntary Clients

Authors: Yu-Chi Liao, Nai-Wen Guo, Chun‑Hung Lee, Yung-Chin Lu, Cheng-Hung Ko

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Objective: The incidence of behavioral addictions, especially substance use disorders (SUDs), is gradually be taken seriously with various physical health problems. Mindfulness-based relapse prevention (MBRP) is a treatment option for promoting long-term health behavior change in recent years. MBRP is a structured protocol that integrates formal meditation practices with the cognitive-behavioral approach of relapse prevention treatment by teaching participants not to engage in reappraisal or savoring techniques. However, considering SUDs as a complex brain disease, questionnaires and symptom evaluation are not sufficient to evaluate the effect of MBRP. Neurophysiological biomarkers such as quantitative electroencephalogram (QEEG) may improve accurately represent the curative effects. This study attempted to find out the neurophysiological indicator of MBRP in various severity SUD involuntary clients. Participants and Methods: Thirteen participants (all males) completed 8-week mindfulness-based treatment provided by trained, licensed clinical psychologists. The behavioral data were from the Severity of Dependence Scale (SDS) and Negative Mood Regulation Scale (NMR) before and afterMBRP treatment. The QEEG data were simultaneously recorded with executive attention tasks, called comprehensive nonverbal attention test(CNAT). The two-way repeated-measures (treatment * severity) ANOVA and independent t-test were used for statistical analysis. Results: Thirteen participants regrouped into high substance dependence (HS) and low substance dependence (LS) by SDS cut-off. The HS group showed more SDS total score and lower gamma wave in the Go/No Go task of CNAT at pretest. Both groups showed the main effect that they had a lower frontal theta/beta ratio (TBR) during the simple reaction time task of CNAT. The main effect showed that the delay errors of CNAT were lower after MBRP. There was no other difference in CNAT between groups. However, after MBRP, compared to LS, the HS group have resonant progress in improving SDS and NMR scores. The neurophysiological index, the frontal TBR of the HS during the Go/No Go task of CNATdecreased than that of the LS group. Otherwise, the LS group’s gamma wave was a significant reduction on the Go/No Go task of CNAT. Conclusion: The QEEG data supports the MBRP can restore the prefrontal function of involuntary addicts and lower their errors in executive attention tasks. However, the improvement of MBRPfor the addict with high addiction severity is significantly more than that with low severity, including QEEG’s indicators and negative emotion regulation. Future directions include investigating the reasons for differences in efficacy among different severity of the addiction.

Keywords: mindfulness, involuntary clients, QEEG, emotion regulation

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581 Indeterminacy: An Urban Design Tool to Measure Resilience to Climate Change, a Caribbean Case Study

Authors: Tapan Kumar Dhar

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How well are our city forms designed to adapt to climate change and its resulting uncertainty? What urban design tools can be used to measure and improve resilience to climate change, and how would they do so? In addressing these questions, this paper considers indeterminacy, a concept originated in the resilience literature, to measure the resilience of built environments. In the realm of urban design, ‘indeterminacy’ can be referred to as built-in design capabilities of an urban system to serve different purposes which are not necessarily predetermined. An urban system, particularly that with a higher degree of indeterminacy, can enable the system to be reorganized and changed to accommodate new or unknown functions while coping with uncertainty over time. Underlying principles of this concept have long been discussed in the urban design and planning literature, including open architecture, landscape urbanism, and flexible housing. This paper argues that the concept indeterminacy holds the potential to reduce the impacts of climate change incrementally and proactively. With regard to sustainable development, both planning and climate change literature highly recommend proactive adaptation as it involves less cost, efforts, and energy than last-minute emergency or reactive actions. Nevertheless, the concept still remains isolated from resilience and climate change adaptation discourses even though the discourses advocate the incremental transformation of a system to cope with climatic uncertainty. This paper considers indeterminacy, as an urban design tool, to measure and increase resilience (and adaptive capacity) of Long Bay’s coastal settlements in Negril, Jamaica. Negril is one of the popular tourism destinations in the Caribbean highly vulnerable to sea-level rise and its associated impacts. This paper employs empirical information obtained from direct observation and informal interviews with local people. While testing the tool, this paper deploys an urban morphology study, which includes land use patterns and the physical characteristics of urban form, including street networks, block patterns, and building footprints. The results reveal that most resorts in Long Bay are designed for pre-determined purposes and offer a little potential to use differently if needed. Additionally, Negril’s street networks are found to be rigid and have limited accessibility to different points of interest. This rigidity can expose the entire infrastructure further to extreme climatic events and also impedes recovery actions after a disaster. However, Long Bay still has room for future resilient developments in other relatively less vulnerable areas. In adapting to climate change, indeterminacy can be reached through design that achieves a balance between the degree of vulnerability and the degree of indeterminacy: the more vulnerable a place is, the more indeterminacy is useful. This paper concludes with a set of urban design typologies to increase the resilience of coastal settlements.

Keywords: climate change adaptation, resilience, sea-level rise, urban form

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580 Construction of a Dynamic Migration Model of Extracellular Fluid in Brain for Future Integrated Control of Brain State

Authors: Tomohiko Utsuki, Kyoka Sato

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In emergency medicine, it is recognized that brain resuscitation is very important for the reduction of mortality rate and neurological sequelae. Especially, the control of brain temperature (BT), intracranial pressure (ICP), and cerebral blood flow (CBF) are most required for stabilizing brain’s physiological state in the treatment for such as brain injury, stroke, and encephalopathy. However, the manual control of BT, ICP, and CBF frequently requires the decision and operation of medical staff, relevant to medication and the setting of therapeutic apparatus. Thus, the integration and the automation of the control of those is very effective for not only improving therapeutic effect but also reducing staff burden and medical cost. For realizing such integration and automation, a mathematical model of brain physiological state is necessary as the controlled object in simulations, because the performance test of a prototype of the control system using patients is not ethically allowed. A model of cerebral blood circulation has already been constructed, which is the most basic part of brain physiological state. Also, a migration model of extracellular fluid in brain has been constructed, however the condition that the total volume of intracranial cavity is almost changeless due to the hardness of cranial bone has not been considered in that model. Therefore, in this research, the dynamic migration model of extracellular fluid in brain was constructed on the consideration of the changelessness of intracranial cavity’s total volume. This model is connectable to the cerebral blood circulation model. The constructed model consists of fourteen compartments, twelve of which corresponds to perfused area of bilateral anterior, middle and posterior cerebral arteries, the others corresponds to cerebral ventricles and subarachnoid space. This model enable to calculate the migration of tissue fluid from capillaries to gray matter and white matter, the flow of tissue fluid between compartments, the production and absorption of cerebrospinal fluid at choroid plexus and arachnoid granulation, and the production of metabolic water. Further, the volume, the colloid concentration, and the tissue pressure of/in each compartment are also calculable by solving 40-dimensional non-linear simultaneous differential equations. In this research, the obtained model was analyzed for its validation under the four condition of a normal adult, an adult with higher cerebral capillary pressure, an adult with lower cerebral capillary pressure, and an adult with lower colloid concentration in cerebral capillary. In the result, calculated fluid flow, tissue volume, colloid concentration, and tissue pressure were all converged to suitable value for the set condition within 60 minutes at a maximum. Also, because these results were not conflict with prior knowledge, it is certain that the model can enough represent physiological state of brain under such limited conditions at least. One of next challenges is to integrate this model and the already constructed cerebral blood circulation model. This modification enable to simulate CBF and ICP more precisely due to calculating the effect of blood pressure change to extracellular fluid migration and that of ICP change to CBF.

Keywords: dynamic model, cerebral extracellular migration, brain resuscitation, automatic control

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579 Injunctions, Disjunctions, Remnants: The Reverse of Unity

Authors: Igor Guatelli

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The universe of aesthetic perception entails impasses about sensitive divergences that each text or visual object may be subjected to. If approached through intertextuality that is not based on the misleading notion of kinships or similarities a priori admissible, the possibility of anachronistic, heterogeneous - and non-diachronic - assemblies can enhance the emergence of interval movements, intermediate, and conflicting, conducive to a method of reading, interpreting, and assigning meaning that escapes the rigid antinomies of the mere being and non-being of things. In negative, they operate in a relationship built by the lack of an adjusted meaning set by their positive existences, with no remainders; the generated interval becomes the remnant of each of them; it is the opening that obscures the stable positions of each one. Without the negative of absence, of that which is always missing or must be missing in a text, concept, or image made positive by history, nothing is perceived beyond what has been already given. Pairings or binary oppositions cannot lead only to functional syntheses; on the contrary, methodological disturbances accumulated by the approximation of signs and entities can initiate a process of becoming as an opening to an unforeseen other, transformation until a moment when the difficulties of [re]conciliation become the mainstay of a future of that sign/entity, not envisioned a priori. A counter-history can emerge from these unprecedented, misadjusted approaches, beginnings of unassigned injunctions and disjunctions, in short, difficult alliances that open cracks in a supposedly cohesive history, chained in its apparent linearity with no remains, understood as a categorical historical imperative. Interstices are minority fields that, because of their opening, are capable of causing opacity in that which, apparently, presents itself with irreducible clarity. Resulting from an incomplete and maladjusted [at the least dual] marriage between the signs/entities that originate them, this interval may destabilize and cause disorder in these entities and their own meanings. The interstitials offer a hyphenated relationship: a simultaneous union and separation, a spacing between the entity’s identity and its otherness or, alterity. One and the other may no longer be seen without the crack or fissure that now separates them, uniting, by a space-time lapse. Ontological, semantic shifts are caused by this fissure, an absence between one and the other, one with and against the other. Based on an improbable approximation between some conceptual and semantic shifts within the design production of architect Rem Koolhaas and the textual production of the philosopher Jacques Derrida, this article questions the notion of unity, coherence, affinity, and complementarity in the process of construction of thought from these ontological, epistemological, and semiological fissures that rattle the signs/entities and their stable meanings. Fissures in a thought that is considered coherent, cohesive, formatted are the negativity that constitutes the interstices that allow us to move towards what still remains as non-identity, which allows us to begin another story.

Keywords: clearing, interstice, negative, remnant, spectrum

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578 Evaluation of Anti-inflammatory Activities of Extracts Obtained from Capparis Erythrocarpos In-Vivo

Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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577 The Impact of Non State Actor’s to Protect Refugees in Kurdistan Region of Iraq

Authors: Rozh Abdulrahman Kareem

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The displacement of individuals has become a common interest for international players. Mostly occurs in Islamic states, as religion is considered the most common cause of this form of displacement. Therefore, this thesis aims to depict the reality of the situations of the refugees, particularly in KRI, illustrating how they are treated and protected and if the treatment merits the protection clause as envisaged in the 1951 Refugee Convention. Overall, the aim is to touch on the issue of protection by non-governmental organizations and government towards the refugees here. In light of this, it focused on the adequate protection of refugees in relation to the refugee law. In the Middle East, including Iraq, there have been multiple reports on violations of these refugee laws and human rights. Protection involves providing physical security to the concerned parties, functional administration with legal structures, and infrastructural setup that could help citizens exercise rights. The KRI has provided the refugees with various benefits, including education, access to residency, and employment. It also provided transitionary in various social dimensions like gender-based violence. The Convention on Status of Refugees 1951 tried to resolve this problem, whereby the principle of ‘nonrefoulement’ under Article 33 was passed. The ‘nonrefoulement’, an exceptional reference, was enacted to protect refugees from forcible return to their countries of the original. However, the convention never addressed an unusual scenario regarding the application of this principle, ‘Extradition Treaties.’ Even though some scholarly article exists regarding the problems of refugees, the topic of interplay between Nonrefoulement and Extradition Treaties has never been explained in detail in the available books on refugee laws and practices. Each year, millions of refugees seek protection from foreign countries for fear of being tortured, victimized, or executed. People seeking international protection are susceptible and insecure. The main objective of the prevention is to provide security to citizens susceptible to inhuman treatment, distress, oppression, or other human rights defilements when they arrive back in their own countries. The refugee situation may get worse in the near future. Just like several nations within the Middle East, Iraq is not a signatory to the globally acknowledged legal structure for the protection of refugees. The first law of 1971 in Iraq was issued only for military or political causes. This law also establishes benefits such as the right to education and health services and the right to acquire employment just as the Iraqi nationals. The other legislative instrument is the 21st law from the ministry of migration of Iraq widened the description of an immigrant to incorporate the definition from the refugee resolution. Nonetheless, there is a lack of overall consistency in the protection provided under these legislations regarding rights and entitlement. A Memorandum of Understanding was signed in October 2016 by the UNHCR and the Iraq government to develop the protection of refugees. Under the term of this MoU, the Iraqi Government is obligated to provide identity documents to asylum seekers beside that UNHCR provides more guidance.

Keywords: law, refugee, protection, Kurdistan

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576 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: deconvolution, imaging, microenvironment, PDAC

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575 Need for Elucidation of Palaeoclimatic Variability in the High Himalayan Mountains: A Multiproxy Approach

Authors: Sheikh Nawaz Ali, Pratima Pandey, P. Morthekai, Jyotsna Dubey, Md. Firoze Quamar

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The high mountain glaciers are one of the most sensitive recorders of climate changes, because they have the tendency to respond to the combined effect of snow fall and temperature. The Himalayan glaciers have been studied with a good pace during the last decade. However, owing to its large ecological diversity and geographical vividness, major part of the Indian Himalaya is uninvestigated, and hence the palaeoclimatic patterns as well as the chronology of past glaciations in particular remain controversial for the entire Indian Himalayan transect. Although the Himalayan glaciers are nourished by two important climatic systems viz. the southwest summer monsoon and the mid-latitude westerlies, however, the influence of these systems is yet to be understood. Nevertheless, existing chronology (mostly exposure ages) indicate that irrespective of the geographical position, glaciers seem to grow during enhanced Indian summer monsoon (ISM). The Himalayan mountain glaciers are referred to the third pole or water tower of Asia as they form a huge reservoir of the fresh water supplies for the Asian countries. Mountain glaciers are sensitive probes of the local climate, and, thus, they present an opportunity and a challenge to interpret climates of the past as well as to predict future changes. The principle object of all the palaeoclimatic studies is to develop a futuristic models/scenario. However, it has been found that the glacial chronologies bracket the major phases of climatic events only, and other climatic proxies are sparse in Himalaya. This is the reason that compilation of data for rapid climatic change during the Holocene shows major gaps in this region. The sedimentation in proglacial lakes, conversely, is more continuous and, hence, can be used to reconstruct a more complete record of past climatic variability that is modulated by changing ice volume of the valley glacier. The Himalayan region has numerous proglacial lacustrine deposits formed during the late Quaternary period. However, there are only few such deposits which have been studied so far. Therefore, this is the high time when efforts have to be made to systematically map the moraines located in different climatic zones, reconstruct the local and regional moraine stratigraphy and use multiple dating techniques to bracket the events of glaciation. Besides this, emphasis must be given on carrying multiproxy studies on the lacustrine sediments that will provide a high resolution palaeoclimatic data from the alpine region of the Himalaya. Although the Himalayan glaciers fluctuated in accordance with the changing climatic conditions (natural forcing), however, it is too early to arrive at any conclusion. It is very crucial to generate multiproxy data sets covering wider geographical and ecological domains taking into consideration multiple parameters that directly or indirectly influence the glacier mass balance as well as the local climate of a region.

Keywords: glacial chronology, palaeoclimate, multiproxy, Himalaya

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574 Artificial Neural Network and Satellite Derived Chlorophyll Indices for Estimation of Wheat Chlorophyll Content under Rainfed Condition

Authors: Muhammad Naveed Tahir, Wang Yingkuan, Huang Wenjiang, Raheel Osman

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Numerous models used in prediction and decision-making process but most of them are linear in natural environment, and linear models reach their limitations with non-linearity in data. Therefore accurate estimation is difficult. Artificial Neural Networks (ANN) found extensive acceptance to address the modeling of the complex real world for the non-linear environment. ANN’s have more general and flexible functional forms than traditional statistical methods can effectively deal with. The link between information technology and agriculture will become more firm in the near future. Monitoring crop biophysical properties non-destructively can provide a rapid and accurate understanding of its response to various environmental influences. Crop chlorophyll content is an important indicator of crop health and therefore the estimation of crop yield. In recent years, remote sensing has been accepted as a robust tool for site-specific management by detecting crop parameters at both local and large scales. The present research combined the ANN model with satellite-derived chlorophyll indices from LANDSAT 8 imagery for predicting real-time wheat chlorophyll estimation. The cloud-free scenes of LANDSAT 8 were acquired (Feb-March 2016-17) at the same time when ground-truthing campaign was performed for chlorophyll estimation by using SPAD-502. Different vegetation indices were derived from LANDSAT 8 imagery using ERADAS Imagine (v.2014) software for chlorophyll determination. The vegetation indices were including Normalized Difference Vegetation Index (NDVI), Green Normalized Difference Vegetation Index (GNDVI), Chlorophyll Absorbed Ratio Index (CARI), Modified Chlorophyll Absorbed Ratio Index (MCARI) and Transformed Chlorophyll Absorbed Ratio index (TCARI). For ANN modeling, MATLAB and SPSS (ANN) tools were used. Multilayer Perceptron (MLP) in MATLAB provided very satisfactory results. For training purpose of MLP 61.7% of the data, for validation purpose 28.3% of data and rest 10% of data were used to evaluate and validate the ANN model results. For error evaluation, sum of squares error and relative error were used. ANN model summery showed that sum of squares error of 10.786, the average overall relative error was .099. The MCARI and NDVI were revealed to be more sensitive indices for assessing wheat chlorophyll content with the highest coefficient of determination R²=0.93 and 0.90 respectively. The results suggested that use of high spatial resolution satellite imagery for the retrieval of crop chlorophyll content by using ANN model provides accurate, reliable assessment of crop health status at a larger scale which can help in managing crop nutrition requirement in real time.

Keywords: ANN, chlorophyll content, chlorophyll indices, satellite images, wheat

Procedia PDF Downloads 146
573 Birth Weight, Weight Gain and Feeding Pattern as Predictors for the Onset of Obesity in School Children

Authors: Thimira Pasas P, Nirmala Priyadarshani M, Ishani R

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Obesity is a global health issue. Early identification is essential to plan interventions and intervene than to reduce the worsening of obesity and its consequences on the health issues of the individual. Childhood obesity is multifactorial, with both modifiable and unmodifiable risk factors. A genetically susceptible individual (unmodifiable), when placed in an obesogenic environment (modifiable), is likely to become obese in onset and progression. The present study was conducted to identify the age of onset of childhood obesity and the influence of modifiable risk factors for childhood obesity among school children living in a suburban area of Sri Lanka. The study population was aged 11-12 years of Piliyandala Educational Zone. Data were collected from 11–12-year-old school children attending government schools in the Piliyandala Educational Zone. They were using a validated, pre-tested self-administered questionnaire. A stratified random sampling method was performed to select schools and to select a representative sample to include all 3 types of government schools of students due to the prevailing pandemic situation, information from the last school medical inspection on data from 2020used for this purpose. For each obese child identified, 2 non-obese children were selected as controls. A single representative from the area was selected by using a systematic random sampling method with a sampling interval of 3. Data was collected using a validated, pre-tested self-administered questionnaire and the Child Health Development Record of the child. An introduction, which included explanations and instructions for filing the questionnaire, was carried out as a group activity prior to distributing the questionnaire among the sample. The results of the present study aligned with the hypothesis that the age of onset of childhood obesity and prediction must be within the first two years of child life. A total of 130 children (66 males: 64 females) participated in the study. The age of onset of obesity was seen to be within the first two years of life. The risk of obesity at 11-12 years of age was Obesity risk was identified at 3-time s higher among females who underwent rapid weight gain within their infancy period. Consuming milk prior to breakfast emerged as a risk factor that increases the risk of obesity by three times. The current study found that the drink before breakfast tends to increase the obesity risk by 3-folds, especially among obese females. Proper monitoring must be carried out to identify the rapid weight gain, especially within the first 2 years of life. Consumption of mug milk before breakfast tends to increase the obesity risk by 3 times. Identification of the confounding factors, proper awareness of the mothers/guardians and effective proper interventions need to be carried out to reduce the obesity risk among school children in the future.

Keywords: childhood obesity, school children, age of onset, weight gain, feeding pattern, activity level

Procedia PDF Downloads 139
572 Biotechnology Approach: A Tool of Enhancement of Sticky Mucilage of Pulicaria Incisa (Medicinal Plant) for Wounds Treatment

Authors: Djamila Chabane, Asma Rouane, Karim Arab

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Depending of the chemical substances responsible for the pharmacological effects, a future therapeutic drug might be produced by extraction from whole plants or by callus initiated from some parts. The optimized callus culture protocols now offer the possibility to use cell culture techniques for vegetative propagation and open minds for further studies on secondary metabolites and drug establishment. In Algerian traditional medicine, Pulicaria incisa (Asteraceae) is used in the treatment of daily troubles (stomachache, headhache., cold, sore throat and rheumatic arthralgia). Field findings revealed that many healers use some fresh parts (leaves, flowers) of this plant to treat skin wounds. This study aims to evaluate the healing efficiency of artisanal cream prepared from sticky mucilage isolated from calluses on dermal wounds of animal models. Callus cultures were initiated from reproductive explants (young inflorescences) excised from adult plants and transferred to a MS basal medium supplemented with growth regulators and maintained under dark for for months. Many calluses types were obtained with various color and aspect (friable, compact). Several subcultures of calli were performed to enhance the mucilage accumulation. After extraction, the mucilage extracts were tested on animal models as follows. The wound healing potential was studied by causing dermal wounds (1 cm diameter) at the dorsolumbar part of Rattus norvegicus; different samples of the cream were applied after hair removal on three rats each, including two controls (one treated by Vaseline and one without any treatment), two experimental groups (experimental group 1, treated with a reference ointment "Madecassol® and experimental group 2 treated by callus mucilage cream for a period of seventeen days. The evolution of the healing activity was estimated by calculating the percentage reduction of the area wounds treated by all compounds tested compared to the controls by using AutoCAD software. The percentage of healing effect of the cream prepared from callus mucilage was (99.79%) compared to that of Madecassol® (99.76%). For the treatment time, the significant healing activity was observed after 17 days compared to that of the reference pharmaceutical products without any wound infection. The healing effect of Madecassol® is more effective because it stimulates and regulates the production of collagen, a fibrous matrix essential for wound healing. Mucilage extracts also showed a high capacity to heal the skin without any infection. According to this pharmacological activity, we suggest to use calluses produced by in vitro culture to producing new compounds for the skin care and treatment.

Keywords: calluses, Pulicaria incisa, mucilage, Wounds

Procedia PDF Downloads 127
571 Network Impact of a Social Innovation Initiative in Rural Areas of Southern Italy

Authors: A. M. Andriano, M. Lombardi, A. Lopolito, M. Prosperi, A. Stasi, E. Iannuzzi

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In according to the scientific debate on the definition of Social Innovation (SI), the present paper identifies SI as new ideas (products, services, and models) that simultaneously meet social needs and create new social relationships or collaborations. This concept offers important tools to unravel the difficult condition for the agricultural sector in marginalized areas, characterized by the abandonment of activities, low level of farmer education, and low generational renewal, hampering new territorial strategies addressed at and integrated and sustainable development. Models of SI in agriculture, starting from bottom up approach or from the community, are considered to represent the driving force of an ecological and digital revolution. A system based on SI may be able to grasp and satisfy individual and social needs and to promote new forms of entrepreneurship. In this context, Vazapp ('Go Hoeing') is an emerging SI model in southern Italy that promotes solutions for satisfying needs of farmers and facilitates their relationships (creation of network). The Vazapp’s initiative, considered in this study, is the Contadinners ('Farmer’s dinners'), a dinner held at farmer’s house where stakeholders living in the surrounding area know each other and are able to build a network for possible future professional collaborations. The aim of the paper is to identify the evolution of farmers’ relationships, both quantitatively and qualitatively, because of the Contadinner’s initiative organized by Vazapp. To this end, the study adopts the Social Network Analysis (SNA) methodology by using UCINET (Version 6.667) software to analyze the relational structure. Data collection was realized through a questionnaire distributed to 387 participants in the twenty 'Contadinners', held from February 2016 to June 2018. The response rate to the survey was about 50% of farmers. The elaboration data was focused on different aspects, such as: a) the measurement of relational reciprocity among the farmers using the symmetrize method of answers; b) the measurement of the answer reliability using the dichotomize method; c) the description of evolution of social capital using the cohesion method; d) the clustering of the Contadinners' participants in followers and not-followers of Vazapp to evaluate its impact on the local social capital. The results concern the effectiveness of this initiative in generating trustworthy relationships within the rural area of southern Italy, typically affected by individualism and mistrust. The number of relationships represents the quantitative indicator to define the dimension of the network development; while the typologies of relationships (from simple friendship to formal collaborations, for branding new cooperation initiatives) represents the qualitative indicator that offers a diversified perspective of the network impact. From the analysis carried out, Vazapp’s initiative represents surely a virtuous SI model to catalyze the relationships within the rural areas and to develop entrepreneurship based on the real needs of the community.

Keywords:

Procedia PDF Downloads 110
570 Organic Rankine Cycles (ORC) for Mobile Applications: Economic Feasibility in Different Transportation Sectors

Authors: Roberto Pili, Alessandro Romagnoli, Hartmut Spliethoff, Christoph Wieland

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Internal combustion engines (ICE) are today the most common energy system to drive vehicles and transportation systems. Numerous studies state that 50-60% of the fuel energy content is lost to the ambient as sensible heat. ORC offers a valuable alternative to recover such waste heat from ICE, leading to fuel energy savings and reduced emissions. In contrast, the additional weight of the ORC affects the net energy balance of the overall system and the ORC occupies additional volume that competes with vehicle transportation capacity. Consequently, a lower income from delivered freight or passenger tickets can be achieved. The economic feasibility of integrating an ORC into an ICE and the resulting economic impact of weight and volume have not been analyzed in open literature yet. This work intends to define such a benchmark for ORC applications in the transportation sector and investigates the current situation on the market. The applied methodology refers to the freight market, but it can be extended to passenger transportation as well. The economic parameter X is defined as the ratio between the variation of the freight revenues and the variation of fuel costs when an ORC is installed as a bottoming cycle for an ICE with respect to a reference case without ORC. A good economic situation is obtained when the reduction in fuel costs is higher than the reduction of revenues for the delivered freight, i.e. X<1. Through this constraint, a maximum allowable change of transport capacity for a given relative reduction in fuel consumption is determined. The specific fuel consumption is influenced by the ORC in two ways. Firstly because the transportable freight is reduced and secondly because the total weight of the vehicle is increased. Note, that the generated electricity of the ORC influences the size of the ICE and the fuel consumption as well. Taking the above dependencies into account, the limiting condition X = 1 results in a second order equation for the relative change in transported cargo. The described procedure is carried out for a typical city bus, a truck of 24-40 t of payload capacity, a middle-size freight train (1000 t), an inland water vessel (Va RoRo, 2500 t) and handysize-like vessel (25000 t). The maximum allowable mass and volume of the ORC are calculated in dependence of its efficiency in order to satisfy X < 1. Subsequently, these values are compared with weight and volume of commercial ORC products. For ships of any size, the situation appears already highly favorable. A different result is obtained for road and rail vehicles. For trains, the mass and the volume of common ORC products have to be reduced at least by 50%. For trucks and buses, the situation looks even worse. The findings of the present study show a theoretical and practical approach for the economic application of ORC in the transportation sector. In future works, the potential for volume and mass reduction of the ORC will be addressed, together with the integration of an economic assessment for the ORC.

Keywords: ORC, transportation, volume, weight

Procedia PDF Downloads 225
569 Edge Enhancement Visual Methodology for Fat Amount and Distribution Assessment in Dry-Cured Ham Slices

Authors: Silvia Grassi, Stefano Schiavon, Ernestina Casiraghi, Cristina Alamprese

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Dry-cured ham is an uncooked meat product particularly appreciated for its peculiar sensory traits among which lipid component plays a key role in defining quality and, consequently, consumers’ acceptability. Usually, fat content and distribution are chemically determined by expensive, time-consuming, and destructive analyses. Moreover, different sensory techniques are applied to assess product conformity to desired standards. In this context, visual systems are getting a foothold in the meat market envisioning more reliable and time-saving assessment of food quality traits. The present work aims at developing a simple but systematic and objective visual methodology to assess the fat amount of dry-cured ham slices, in terms of total, intermuscular and intramuscular fractions. To the aim, 160 slices from 80 PDO dry-cured hams were evaluated by digital image analysis and Soxhlet extraction. RGB images were captured by a flatbed scanner, converted in grey-scale images, and segmented based on intensity histograms as well as on a multi-stage algorithm aimed at edge enhancement. The latter was performed applying the Canny algorithm, which consists of image noise reduction, calculation of the intensity gradient for each image, spurious response removal, actual thresholding on corrected images, and confirmation of strong edge boundaries. The approach allowed for the automatic calculation of total, intermuscular and intramuscular fat fractions as percentages of the total slice area. Linear regression models were run to estimate the relationships between the image analysis results and the chemical data, thus allowing for the prediction of the total, intermuscular and intramuscular fat content by the dry-cured ham images. The goodness of fit of the obtained models was confirmed in terms of coefficient of determination (R²), hypothesis testing and pattern of residuals. Good regression models have been found being 0.73, 0.82, and 0.73 the R2 values for the total fat, the sum of intermuscular and intramuscular fat and the intermuscular fraction, respectively. In conclusion, the edge enhancement visual procedure brought to a good fat segmentation making the simple visual approach for the quantification of the different fat fractions in dry-cured ham slices sufficiently simple, accurate and precise. The presented image analysis approach steers towards the development of instruments that can overcome destructive, tedious and time-consuming chemical determinations. As future perspectives, the results of the proposed image analysis methodology will be compared with those of sensory tests in order to develop a fast grading method of dry-cured hams based on fat distribution. Therefore, the system will be able not only to predict the actual fat content but it will also reflect the visual appearance of samples as perceived by consumers.

Keywords: dry-cured ham, edge detection algorithm, fat content, image analysis

Procedia PDF Downloads 173
568 Comparative Chromatographic Profiling of Wild and Cultivated Macrocybe Gigantea (Massee) Pegler & Lodge

Authors: Gagan Brar, Munruchi Kaur

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Macrocybe gigantea was collected from the wild, growing as pure white, fleshy, robust fruit bodies in caespitose clusters. Initially, the few ladies collecting these fruiting bodies for cooking revealed their edibility status, which was later confirmed through classical and molecular taxonomy. The culture of this potential wild edible taxa was raised with an aim of domesticating it. Various solid and liquid media were evaluated for their vegetative growth, in which Malt Extract Agar was found to be the best solid medium and Glucose Peptone medium as the best liquid medium. The effect of different temperatures as well as pH was also evaluated for the vegetative growth of M. gigantea, and it was found that it shows maximum vegetative growth at 30° and pH 5. For spawn preparation, various grains viz. Wheat grains, Jowar grains, Bajra grains and Maize grains were evaluated, and it was found that wheat grains boiled for 30 minutes gave the maximum mycelial growth. Mother spawn was thus prepared on wheat grains boiled for 30 minutes. For raising the fruiting bodies, different locally available agro-wastes were tried, and it was found that paddy straw gives the best growth. Both wilds as well as cultivated M. gigantea were compared through HPLC to evaluate the different nutritional and nutraceutical values. For the evaluation of different sugars in wild and cultivated M. gigantea, 15 sugars were taken for analysis. Among these Melezitose, Trehalose, Glucose, Xylose and Mannitol were found in the wild collection of M. gigantea; in the cultivated sample, Melezitose, Trehalose, Xylose and Dulcitol were detected. Among the 20 different amino acids, 18 amino acids were found, except Asparagine and Glutamine in both wild as well as cultivated samples. Among the 37 tested fatty acids, only 6 fatty acids, namely Palmitic acid, Stearic acid, Cis-9 Oleic acid, Linoleic acid, Gamma-Linolenic acid and Tricosanoic acid, were found in both wild and cultivated samples, although the concentration of these fatty acids was more in the cultivated sample. From the various vitamins tested, Vitamin C, D and E were present in both wild and cultivated samples. Both wild as well as cultivated samples were evaluated for the presence of phenols; for this purpose, eleven phenols were taken as standards in HPLC analysis, and it was found that Gallic acid, Resorcinol, Ferulic acid and Pyrogallol were present in the wild mushroom sample whereas in the cultivated sample Ferulic acid, Caffeic Acid, Vanillic acid and Vanillin are present. The flavonoid analysis revealed the presence of Rutin, Naringin and Quercetin in wild M. gigantea, while 5 Naringin, Catechol, Myrecetin, Gossypin and Quercetin were found in cultivated one. From the comparative chromatographic profiling of both wild as well as cultivated M. gigantea, it is concluded that no nutrient loss was found during its cultivation. An increase in percentage of secondary metabolites (i.e., phenols and flavonoids) was found in cultivated one as compared to wild M. gigantea. Thus, from future perspective cultivated species of M. gigantea can be recommended for the commercial purpose as a good food supplement.

Keywords: culture, edible, fruit bodies, wild

Procedia PDF Downloads 69
567 Using Human-Centred Service Design and Partnerships as a Model to Promote Cross-Sector Social Responsibility in Disaster Resilience: An Australian Case Study

Authors: Keith Diamond, Tracy Collier, Ciara Sterling, Ben Kraal

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The increased frequency and intensity of disaster events in the Asia-Pacific region is likely to require organisations to better understand how their initiatives, and the support they provide to their customers, intersect with other organisations aiming to support communities in achieving disaster resilience. While there is a growing awareness that disaster response and recovery rebuild programmes need to adapt to more integrated, community-led approaches, there is often a discrepancy between how programmes intend to work and how they are collectively experienced in the community, creating undesired effects on community resilience. Following Australia’s North Queensland Monsoon Disaster of 2019, this research set out to understand and evaluate how the service and support ecosystem impacted on the local community’s experience and influenced their ability to respond and recover. The purpose of this initiative was to identify actionable, cross-sector, people-centered improvements that support communities to recover and thrive when faced with disaster. The challenge arose as a group of organisations, including utility providers, banks, insurers, and community organisations, acknowledged that improving their own services would have limited impact on community wellbeing unless the other services people need are also improved and aligned. The research applied human-centred service design methods, typically applied to single products or services, to design a new way to understand a whole-of-community journey. Phase 1 of the research conducted deep contextual interviews with residents and small business owners impacted by the North Queensland Monsoon and qualitative data was analysed to produce community journey maps that detailed how individuals navigated essential services, such as accommodation, finance, health, and community. Phase 2 conducted interviews and focus groups with frontline workers who represented industries that provided essential services to assist the community. Data from Phase 1 and Phase 2 of the research was analysed and combined to generate a systems map that visualised the positive and negative impacts that occurred across the disaster response and recovery service ecosystem. Insights gained from the research has catalysed collective action to address future Australian disaster events. The case study outlines a transformative way for sectors and industries to rethink their corporate social responsibility activities towards a cross-sector partnership model that shares responsibility and approaches disaster response and recovery as a single service that can be designed to meet the needs of communities.

Keywords: corporate social responsibility, cross sector partnerships, disaster resilience, human-centred design, service design, systems change

Procedia PDF Downloads 154
566 Correlation between the Levels of Some Inflammatory Cytokines/Haematological Parameters and Khorana Scores of Newly Diagnosed Ambulatory Cancer Patients

Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

Procedia PDF Downloads 80
565 India’s Energy Transition, Pathways for Green Economy

Authors: B. Sudhakara Reddy

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In modern economy, energy is fundamental to virtually every product and service in use. It has been developed on the dependence of abundant and easy-to-transform polluting fossil fuels. On one hand, increase in population and income levels combined with increased per capita energy consumption requires energy production to keep pace with economic growth, and on the other, the impact of fossil fuel use on environmental degradation is enormous. The conflicting policy objectives of protecting the environment while increasing economic growth and employment has resulted in this paradox. Hence, it is important to decouple economic growth from environmental degeneration. Hence, the search for green energy involving affordable, low-carbon, and renewable energies has become global priority. This paper explores a transition to a sustainable energy system using the socio-economic-technical scenario method. This approach takes into account the multifaceted nature of transitions which not only require the development and use of new technologies, but also of changes in user behaviour, policy and regulation. The scenarios that are developed are: baseline business as usual (BAU) as well as green energy (GE). The baseline scenario assumes that the current trends (energy use, efficiency levels, etc.) will continue in future. India’s population is projected to grow by 23% during 2010 –2030, reaching 1.47 billion. The real GDP, as per the model, is projected to grow by 6.5% per year on average between 2010 and 2030 reaching US$5.1 trillion or $3,586 per capita (base year 2010). Due to increase in population and GDP, the primary energy demand will double in two decades reaching 1,397 MTOE in 2030 with the share of fossil fuels remaining around 80%. The increase in energy use corresponds to an increase in energy intensity (TOE/US $ of GDP) from 0.019 to 0.036. The carbon emissions are projected to increase by 2.5 times from 2010 reaching 3,440 million tonnes with per capita emissions of 2.2 tons/annum. However, the carbon intensity (tons per US$ of GDP) decreases from 0.96 to 0.67. As per GE scenario, energy use will reach 1079 MTOE by 2030, a saving of about 30% over BAU. The penetration rate of renewable energy resources will reduce the total primary energy demand by 23% under GE. The reduction in fossil fuel demand and focus on clean energy will reduce the energy intensity to 0.21 (TOE/US$ of GDP) and carbon intensity to 0.42 (ton/US$ of GDP) under the GE scenario. The study develops new ‘pathways out of poverty’ by creating more than 10 million jobs and thus raise the standard of living of low-income people. Our scenarios are, to a great extent, based on the existing technologies. The challenges to this path lie in socio-economic-political domains. However, to attain a green economy the appropriate policy package should be in place which will be critical in determining the kind of investments that will be needed and the incidence of costs and benefits. These results provide a basis for policy discussions on investments, policies and incentives to be put in place by national and local governments.

Keywords: energy, renewables, green technology, scenario

Procedia PDF Downloads 248
564 Technology and the Need for Integration in Public Education

Authors: Eric Morettin

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Cybersecurity and digital literacy are pressing issues among Canadian citizens, yet formal education does not provide today’s students with the necessary knowledge and skills needed to adapt to these challenging issues within the physical and digital labor-market. Canada’s current education systems do not highlight the importance of these respective fields, aside from using technology for learning management systems and alternative methods of assignment completion. Educators are not properly trained to integrate technology into the compulsory courses within public education, to better prepare their learners in these topics and Canada’s digital economy. ICTC addresses these gaps in education and training through cross-Canadian educational programming in digital literacy and competency, cybersecurity and coding which is bridged with Canada’s provincially regulated K-12 curriculum guidelines. After analyzing Canada’s provincial education, it is apparent that there are gaps in learning related to technology, as well as inconsistent educational outcomes that do not adequately represent the current Canadian and global economies. Presently only New Brunswick, Nova Scotia, Ontario, and British Columbia offer curriculum guidelines for cybersecurity, computer programming, and digital literacy. The remaining provinces do not address these skills in their curriculum guidelines. Moreover, certain courses across some provinces not being updated since the 1990’s. The three territories respectfully take curriculum strands from other provinces and use them as their foundation in education. Yukon uses all British Columbia curriculum. Northwest Territories and Nunavut respectfully use a hybrid of Alberta and Saskatchewan curriculum as their foundation of learning. Education that is provincially regulated does not allow for consistency across the country’s educational outcomes and what Canada’s students will achieve – especially when curriculum outcomes have not been updated to reflect present day society. Through this, ICTC has aligned Canada’s provincially regulated curriculum and created opportunities for focused education in the realm of technology to better serve Canada’s present learners and teachers; while addressing inequalities and applicability within curriculum strands and outcomes across the country. As a result, lessons, units, and formal assessment strategies, have been created to benefit students and teachers in this interdisciplinary, cross-curricular, practice - as well as meeting their compulsory education requirements and developing skills and literacy in cyber education. Teachers can access these lessons and units through ICTC’s website, as well as receive professional development regarding the assessment and implementation of these offerings from ICTC’s education coordinators, whose combines experience exceeds 50 years of teaching in public, private, international, and Indigenous schools. We encourage you to take this opportunity that will benefit students and educators, and will bridge the learning and curriculum gaps in Canadian education to better reflect the ever-changing public, social, and career landscape that all citizens are a part of. Students are the future, and we at ICTC strive to ensure their futures are bright and prosperous.

Keywords: cybersecurity, education, curriculum, teachers

Procedia PDF Downloads 82
563 Procedure for Monitoring the Process of Behavior of Thermal Cracking in Concrete Gravity Dams: A Case Study

Authors: Adriana de Paula Lacerda Santos, Bruna Godke, Mauro Lacerda Santos Filho

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Several dams in the world have already collapsed, causing environmental, social and economic damage. The concern to avoid future disasters has stimulated the creation of a great number of laws and rules in many countries. In Brazil, Law 12.334/2010 was created, which establishes the National Policy on Dam Safety. Overall, this policy requires the dam owners to invest in the maintenance of their structures and to improve its monitoring systems in order to provide faster and straightforward responses in the case of an increase of risks. As monitoring tools, visual inspections has provides comprehensive assessment of the structures performance, while auscultation’s instrumentation has added specific information on operational or behavioral changes, providing an alarm when a performance indicator exceeds the acceptable limits. These limits can be set using statistical methods based on the relationship between instruments measures and other variables, such as reservoir level, time of the year or others instruments measuring. Besides the design parameters (uplift of the foundation, displacements, etc.) the dam instrumentation can also be used to monitor the behavior of defects and damage manifestations. Specifically in concrete gravity dams, one of the main causes for the appearance of cracks, are the concrete volumetric changes generated by the thermal origin phenomena, which are associated with the construction process of these structures. Based on this, the goal of this research is to propose a monitoring process of the thermal cracking behavior in concrete gravity dams, through the instrumentation data analysis and the establishment of control values. Therefore, as a case study was selected the Block B-11 of José Richa Governor Dam Power Plant, that presents a cracking process, which was identified even before filling the reservoir in August’ 1998, and where crack meters and surface thermometers were installed for its monitoring. Although these instruments were installed in May 2004, the research was restricted to study the last 4.5 years (June 2010 to November 2014), when all the instruments were calibrated and producing reliable data. The adopted method is based on simple linear correlations procedures to understand the interactions among the instruments time series, verifying the response times between them. The scatter plots were drafted from the best correlations, which supported the definition of the limit control values. Among the conclusions, it is shown that there is a strong or very strong correlation between ambient temperature and the crack meters and flowmeters measurements. Based on the results of the statistical analysis, it was possible to develop a tool for monitoring the behavior of the case study cracks. Thus it was fulfilled the goal of the research to develop a proposal for a monitoring process of the behavior of thermal cracking in concrete gravity dams.

Keywords: concrete gravity dam, dams safety, instrumentation, simple linear correlation

Procedia PDF Downloads 290
562 Monitoring of Vector Mosquitors of Diseases in Areas of Energy Employment Influence in the Amazon (Amapa State), Brazil

Authors: Ribeiro Tiago Magalhães

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Objective: The objective of this study was to evaluate the influence of a hydroelectric power plant in the state of Amapá, and to present the results obtained by dimensioning the diversity of the main mosquito vectors involved in the transmission of pathogens that cause diseases such as malaria, dengue and leishmaniasis. Methodology: The present study was conducted on the banks of the Araguari River, in the municipalities of Porto Grande and Ferreira Gomes in the southern region of Amapá State. Nine monitoring campaigns were conducted, the first in April 2014 and the last in March 2016. The selection of the catch sites was done in order to prioritize areas with possible occurrence of the species considered of greater importance for public health and areas of contact between the wild environment and humans. Sampling efforts aimed to identify the local vector fauna and to relate it to the transmission of diseases. In this way, three phases of collection were established, covering the schedules of greater hematophageal activity. Sampling was carried out using Shannon Shack and CDC types of light traps and by means of specimen collection with the hold method. This procedure was carried out during the morning (between 08:00 and 11:00), afternoon-twilight (between 15:30 and 18:30) and night (between 18:30 and 22:00). In the specific methodology of capture with the use of the CDC equipment, the delimited times were from 18:00 until 06:00 the following day. Results: A total of 32 species of mosquitoes was identified, and a total of 2,962 specimens was taxonomically subdivided into three genera (Culicidae, Psychodidae and Simuliidae) Psorophora, Sabethes, Simulium, Uranotaenia and Wyeomyia), besides those represented by the family Psychodidae that due to the morphological complexities, allows the safe identification (without the method of diaphanization and assembly of slides for microscopy), only at the taxonomic level of subfamily (Phlebotominae). Conclusion: The nine monitoring campaigns carried out provided the basis for the design of the possible epidemiological structure in the areas of influence of the Cachoeira Caldeirão HPP, in order to point out among the points established for sampling, which would represent greater possibilities, according to the group of identified mosquitoes, of disease acquisition. However, what should be mainly considered, are the future events arising from reservoir filling. This argument is based on the fact that the reproductive success of Culicidae is intrinsically related to the aquatic environment for the development of its larvae until adulthood. From the moment that the water mirror is expanded in new environments for the formation of the reservoir, a modification in the process of development and hatching of the eggs deposited in the substrate can occur, causing a sudden explosion in the abundance of some genera, in special Anopheles, which holds preferences for denser forest environments, close to the water portions.

Keywords: Amazon, hydroelectric, power, plants

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561 Spatiotemporal Changes in Drought Sensitivity Captured by Multiple Tree-Ring Parameters of Central European Conifers

Authors: Krešimir Begović, Miloš Rydval, Jan Tumajer, Kristyna Svobodová, Thomas Langbehn, Yumei Jiang, Vojtech Čada, Vaclav Treml, Ryszard Kaczka, Miroslav Svoboda

Abstract:

Environmental changes have increased the frequency and intensity of climatic extremes, particularly hotter droughts, leading to altered tree growth patterns and multi-year lags in tree recovery. The effects of shifting climatic conditions on tree growth are inhomogeneous across species’ natural distribution ranges, with large spatial heterogeneity and inter-population variability, but generally have significant consequences for contemporary forest dynamics and future ecosystem functioning. Despite numerous studies on the impacts of regional drought effects, large uncertainties remain regarding the mechanistic basis of drought legacy effects on wood formation and the ability of individual species to cope with increasingly drier growing conditions and rising year-to-year climatic variability. To unravel the complexity of climate-growth interactions and assess species-specific responses to severe droughts, we combined forward modeling of tree growth (VS-lite model) with correlation analyses against climate (temperature, precipitation, and the SPEI-3 moisture index) and growth responses to extreme drought events from multiple tree-ring parameters (tree-width and blue intensity parameters). We used an extensive dataset with over 1000 tree-ring samples from 23 nature forest reserves across an altitudinal range in Czechia and Slovakia. Our results revealed substantial spatiotemporal variability in growth responses to summer season temperature and moisture availability across species and tree-ring parameters. However, a general trend of increasing spring moisture-growth sensitivity in recent decades was observed in the Scots pine mountain forests and lowland forests of both species. The VS-lite model effectively captured nonstationary climate-growth relationships and accurately estimated high-frequency growth variability, indicating a significant incidence of regional drought events and growth reductions. Notably, growth reductions during extreme drought years and discrete legacy effects identified in individual wood components were most pronounced in the lowland forests. Together with the observed growth declines in recent decades, these findings suggest an increasing vulnerability of Norway spruce and Scots pine in dry lowlands under intensifying climatic constraints.

Keywords: dendroclimatology, Vaganova–Shashkin lite, conifers, central Europe, drought, blue intensity

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560 Statistical Analysis to Compare between Smart City and Traditional Housing

Authors: Taha Anjamrooz, Sareh Rajabi, Ayman Alzaatreh

Abstract:

Smart cities are playing important roles in real life. Integration and automation between different features of modern cities and information technologies improve smart city efficiency, energy management, human and equipment resource management, life quality and better utilization of resources for the customers. One of difficulties in this path, is use, interface and link between software, hardware, and other IT technologies to develop and optimize processes in various business fields such as construction, supply chain management and transportation in parallel to cost-effective and resource reduction impacts. Also, Smart cities are certainly intended to demonstrate a vital role in offering a sustainable and efficient model for smart houses while mitigating environmental and ecological matters. Energy management is one of the most important matters within smart houses in the smart cities and communities, because of the sensitivity of energy systems, reduction in energy wastage and maximization in utilizing the required energy. Specially, the consumption of energy in the smart houses is important and considerable in the economic balance and energy management in smart city as it causes significant increment in energy-saving and energy-wastage reduction. This research paper develops features and concept of smart city in term of overall efficiency through various effective variables. The selected variables and observations are analyzed through data analysis processes to demonstrate the efficiency of smart city and compare the effectiveness of each variable. There are ten chosen variables in this study to improve overall efficiency of smart city through increasing effectiveness of smart houses using an automated solar photovoltaic system, RFID System, smart meter and other major elements by interfacing between software and hardware devices as well as IT technologies. Secondly to enhance aspect of energy management by energy-saving within smart house through efficient variables. The main objective of smart city and smart houses is to reproduce energy and increase its efficiency through selected variables with a comfortable and harmless atmosphere for the customers within a smart city in combination of control over the energy consumption in smart house using developed IT technologies. Initially the comparison between traditional housing and smart city samples is conducted to indicate more efficient system. Moreover, the main variables involved in measuring overall efficiency of system are analyzed through various processes to identify and prioritize the variables in accordance to their influence over the model. The result analysis of this model can be used as comparison and benchmarking with traditional life style to demonstrate the privileges of smart cities. Furthermore, due to expensive and expected shortage of natural resources in near future, insufficient and developed research study in the region, and available potential due to climate and governmental vision, the result and analysis of this study can be used as key indicator to select most effective variables or devices during construction phase and design

Keywords: smart city, traditional housing, RFID, photovoltaic system, energy efficiency, energy saving

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559 Is Liking for Sampled Energy-Dense Foods Mediated by Taste Phenotypes?

Authors: Gary J. Pickering, Sarah Lucas, Catherine E. Klodnicki, Nicole J. Gaudette

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Two taste pheno types that are of interest in the study of habitual diet-related risk factors and disease are 6-n-propylthiouracil (PROP) responsiveness and thermal tasting. Individuals differ considerable in how intensely they experience the bitterness of PROP, which is partially explained by three major single nucleotide polymorphisms associated with the TAS2R38 gene. Importantly, this variable responsiveness is a useful proxy for general taste responsiveness, and links to diet-related disease risk, including body mass index, in some studies. Thermal tasting - a newly discovered taste phenotype independent of PROP responsiveness - refers to the capacity of many individuals to perceive phantom tastes in response to lingual thermal stimulation, and is linked with TRPM5 channels. Thermal tasters (TTs) also experience oral sensations more intensely than thermal non-tasters (TnTs), and this was shown to associate with differences in self-reported food preferences in a previous survey from our lab. Here we report on two related studies, where we sought to determine whether PROP responsiveness and thermal tasting would associate with perceptual differences in the oral sensations elicited by sampled energy-dense foods, and whether in turn this would influence liking. We hypothesized that hyper-tasters (thermal tasters and individuals who experience PROP intensely) would (a) rate sweet and high-fat foods more intensely than hypo-tasters, and (b) would differ from hypo-tasters in liking scores. (Liking has been proposed recently as a more accurate measure of actual food consumption). In Study 1, a range of energy-dense foods and beverages, including table cream and chocolate, was assessed by 25 TTs and 19 TnTs. Ratings of oral sensation intensity and overall liking were obtained using gVAS and gDOL scales, respectively. TTs and TnTs did not differ significantly in intensity ratings for most stimuli (ANOVA). In a 2nd study, 44 female participants sampled 22 foods and beverages, assessing them for intensity of oral sensations (gVAS) and overall liking (9-point hedonic scale). TTs (n=23) rated their overall liking of creaminess and milk products lower than did TnTs (n=21), and liked milk chocolate less. PROP responsiveness was negatively correlated with liking of food and beverages belonging to the sweet or sensory food grouping. No other differences in intensity or liking scores between hyper- and hypo-tasters were found. Taken overall, our results are somewhat unexpected, lending only modest support to the hypothesis that these taste phenotypes associate with energy-dense food liking and consumption through differences in the oral sensations they elicit. Reasons for this lack of concordance with expectations and some prior literature are discussed, and suggestions for future research are advanced.

Keywords: taste phenotypes, sensory evaluation, PROP, thermal tasting, diet-related health risk

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558 A Smart Sensor Network Approach Using Affordable River Water Level Sensors

Authors: Dian Zhang, Brendan Heery, Maria O’Neill, Ciprian Briciu-Burghina, Noel E. O’Connor, Fiona Regan

Abstract:

Recent developments in sensors, wireless data communication and the cloud computing have brought the sensor web to a whole new generation. The introduction of the concept of ‘Internet of Thing (IoT)’ has brought the sensor research into a new level, which involves the developing of long lasting, low cost, environment friendly and smart sensors; new wireless data communication technologies; big data analytics algorithms and cloud based solutions that are tailored to large scale smart sensor network. The next generation of smart sensor network consists of several layers: physical layer, where all the smart sensors resident and data pre-processes occur, either on the sensor itself or field gateway; data transmission layer, where data and instructions exchanges happen; the data process layer, where meaningful information is extracted and organized from the pre-process data stream. There are many definitions of smart sensor, however, to summarize all these definitions, a smart sensor must be Intelligent and Adaptable. In future large scale sensor network, collected data are far too large for traditional applications to send, store or process. The sensor unit must be intelligent that pre-processes collected data locally on board (this process may occur on field gateway depends on the sensor network structure). In this case study, three smart sensing methods, corresponding to simple thresholding, statistical model and machine learning based MoPBAS method, are introduced and their strength and weakness are discussed as an introduction to the smart sensing concept. Data fusion, the integration of data and knowledge from multiple sources, are key components of the next generation smart sensor network. For example, in the water level monitoring system, weather forecast can be extracted from external sources and if a heavy rainfall is expected, the server can send instructions to the sensor notes to, for instance, increase the sampling rate or switch on the sleeping mode vice versa. In this paper, we describe the deployment of 11 affordable water level sensors in the Dublin catchment. The objective of this paper is to use the deployed river level sensor network at the Dodder catchment in Dublin, Ireland as a case study to give a vision of the next generation of a smart sensor network for flood monitoring to assist agencies in making decisions about deploying resources in the case of a severe flood event. Some of the deployed sensors are located alongside traditional water level sensors for validation purposes. Using the 11 deployed river level sensors in a network as a case study, a vision of the next generation of smart sensor network is proposed. Each key component of the smart sensor network is discussed, which hopefully inspires the researchers who are working in the sensor research domain.

Keywords: smart sensing, internet of things, water level sensor, flooding

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557 Vieira Da Silva's Tiles at Universidade Federal Rural Do Rio de Janeiro: A Conservation and Restoration Project

Authors: Adriana Anselmo Oliveira

Abstract:

The present project showcases a tile work from the Franco-Portuguese artist Maria Helena Vieira da Silva (1908-1992). It is a set of 8 panels composed of figurative and geometric tiles, with extra tiles framing nearby doors and windows in a study room in the (UFRRJ, Universidade Federal Rural do Rio de Janeiro). The aforementioned work was created between 1942 and 1943, during the artist's 6 year exile in the Brazilian city. This one-of-a-kind tileset was designed and made by Vieira da Silva between 1942 and 1943. Over the years, several units were lost, which led to their replacement in the nineties. However, these replacements don't do justice to the original work of art. In 2007, a project was initiated to fully repair and maintain the set. Three panels are removed and restored, but the project is halted. To this day, the three fully restored panels remain in boxes. In 2016 a new restoration project is submitted by the (Faculdade de Belas Artes da Universidade de Lisboa) in collaboration with de (Fundacão Árpád Szenes-Vieira da Silva). There are many varied opinions on restoring and conserving older pieces of art, however, we have the moral duty to safeguard the original materials used by the artist along with the artists original vision and also to care for the future generations of students who will use the space in which the tile-work was inserted. Many tiles have been replaced by white tiles, tiles with a divergent colour pallet and technique, and in a few cases, the incorrect place or way around. These many factors make it increasingly difficult to maintain the artists original vision and destroy and chance of coherence within the artwork itself. The conservative technician cannot make new images to fill the empty spaces or mark the remaining images with their own creative input. with reliable photographic documentation that can provide us with the necessary vision to allow us to proceed with an accurate reconstruction, we have the obligation to proceed and return the piece of art to its true form, as in its current state, it is impossible to maintain its original glory. Using the information we have, we must find a way to differentiate the original tiles from the reconstructions in order to recreate and reclaim the original message from the artist. The objective of this project is to understand the significance of tiles in Vieira da Silva's art as well as the influence they had on the artist's pictorial language since the colour definition on tile work is vastly different from the painting process as the materials change during their merger. Another primary goal is to understand what the previous interventions achieved besides increasing the artworks durability. The main objective is to submit a proposal that can salvage the artist's visual intention and supports it for posteriority. In summary, this proposal goes further than the usual conservative interventions as it intends to recreate the original artistic worth, prioritising the aesthetics and keeping its soul alive.

Keywords: Vieira da Silva, tiles, conservation, restoration

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556 Detection, Analysis and Determination of the Origin of Copy Number Variants (CNVs) in Intellectual Disability/Developmental Delay (ID/DD) Patients and Autistic Spectrum Disorders (ASD) Patients by Molecular and Cytogenetic Methods

Authors: Pavlina Capkova, Josef Srovnal, Vera Becvarova, Marie Trkova, Zuzana Capkova, Andrea Stefekova, Vaclava Curtisova, Alena Santava, Sarka Vejvalkova, Katerina Adamova, Radek Vodicka

Abstract:

ASDs are heterogeneous and complex developmental diseases with a significant genetic background. Recurrent CNVs are known to be a frequent cause of ASD. These CNVs can have, however, a variable expressivity which results in a spectrum of phenotypes from asymptomatic to ID/DD/ASD. ASD is associated with ID in ~75% individuals. Various platforms are used to detect pathogenic mutations in the genome of these patients. The performed study is focused on a determination of the frequency of pathogenic mutations in a group of ASD patients and a group of ID/DD patients using various strategies along with a comparison of their detection rate. The possible role of the origin of these mutations in aetiology of ASD was assessed. The study included 35 individuals with ASD and 68 individuals with ID/DD (64 males and 39 females in total), who underwent rigorous genetic, neurological and psychological examinations. Screening for pathogenic mutations involved karyotyping, screening for FMR1 mutations and for metabolic disorders, a targeted MLPA test with probe mixes Telomeres 3 and 5, Microdeletion 1 and 2, Autism 1, MRX and a chromosomal microarray analysis (CMA) (Illumina or Affymetrix). Chromosomal aberrations were revealed in 7 (1 in the ASD group) individuals by karyotyping. FMR1 mutations were discovered in 3 (1 in the ASD group) individuals. The detection rate of pathogenic mutations in ASD patients with a normal karyotype was 15.15% by MLPA and CMA. The frequencies of the pathogenic mutations were 25.0% by MLPA and 35.0% by CMA in ID/DD patients with a normal karyotype. CNVs inherited from asymptomatic parents were more abundant than de novo changes in ASD patients (11.43% vs. 5.71%) in contrast to the ID/DD group where de novo mutations prevailed over inherited ones (26.47% vs. 16.18%). ASD patients shared more frequently their mutations with their fathers than patients from ID/DD group (8.57% vs. 1.47%). Maternally inherited mutations predominated in the ID/DD group in comparison with the ASD group (14.7% vs. 2.86 %). CNVs of an unknown significance were found in 10 patients by CMA and in 3 patients by MLPA. Although the detection rate is the highest when using CMA, recurrent CNVs can be easily detected by MLPA. CMA proved to be more efficient in the ID/DD group where a larger spectrum of rare pathogenic CNVs was revealed. This study determined that maternally inherited highly penetrant mutations and de novo mutations more often resulted in ID/DD without ASD in patients. The paternally inherited mutations could be, however, a source of the greater variability in the genome of the ASD patients and contribute to the polygenic character of the inheritance of ASD. As the number of the subjects in the group is limited, a larger cohort is needed to confirm this conclusion. Inherited CNVs have a role in aetiology of ASD possibly in combination with additional genetic factors - the mutations elsewhere in the genome. The identification of these interactions constitutes a challenge for the future. Supported by MH CZ – DRO (FNOl, 00098892), IGA UP LF_2016_010, TACR TE02000058 and NPU LO1304.

Keywords: autistic spectrum disorders, copy number variant, chromosomal microarray, intellectual disability, karyotyping, MLPA, multiplex ligation-dependent probe amplification

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