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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

Procedia PDF Downloads 51

Authors: Jun Byung Joon, Seo Seok Hyun, Lee Seo Young

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As carbon dioxide emissions increase due to rapid industrialization and reckless development, abnormal climates such as floods and droughts are occurring. In order to respond to such climate change, the use of existing fossil fuels is reduced, and the proportion of eco-friendly renewable energy is gradually increasing. Korea is an energy resource-poor country that depends on imports for 93% of its total energy. As the global energy supply chain instability experienced due to the Russia-Ukraine crisis increases, countries around the world are resetting energy policies to minimize energy dependence and strengthen security. Seawater thermal energy is a renewable energy that replaces the existing air heat energy. It uses the characteristic of having a higher specific heat than air to cool and heat main spaces of buildings to increase heat transfer efficiency and minimize power consumption to generate electricity using fossil fuels, and Carbon dioxide emissions can be minimized. In addition, the effect on the marine environment is very small by using only the temperature characteristics of seawater in a limited way. K-water carried out a demonstration project of supplying cooling and heating energy to spaces such as the central control room and presentation room in the management building by acquiring the heat source of seawater circulated through the power plant's waterway by using the characteristics of the tidal power plant. Compared to the East Sea and the South Sea, the main system was designed in consideration of the large tidal difference, small temperature difference, and low-temperature characteristics, and its performance was verified through operation during the demonstration period. In addition, facility improvements were made for major deficiencies to strengthen monitoring functions, provide user convenience, and improve facility soundness. To spread these achievements, the basic concept was to expand the seawater heating and cooling system with a scale of 200 USRT at the Tidal Culture Center. With the operational experience of the demonstration system, it will be possible to establish an optimal seawater heat cooling and heating system suitable for the characteristics of the west coast ocean. Through this, it is possible to reduce operating costs by KRW 33,31 million per year compared to air heat, and through industry-university-research joint research, it is possible to localize major equipment and materials and develop key element technologies to revitalize the seawater heat business and to advance into overseas markets. The government's efforts are needed to expand the seawater heating and cooling system. Seawater thermal energy utilizes only the thermal energy of infinite seawater. Seawater thermal energy has less impact on the environment than river water thermal energy, except for environmental pollution factors such as bottom dredging, excavation, and sand or stone extraction. Therefore, it is necessary to increase the sense of speed in project promotion by innovatively simplifying unnecessary licensing/permission procedures. In addition, support should be provided to secure business feasibility by dramatically exempting the usage fee of public waters to actively encourage development in the private sector.

Keywords: seawater thermal energy, marine energy, tidal power plant, energy consumption

Procedia PDF Downloads 72

Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler

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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.

Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids

Procedia PDF Downloads 91

Authors: Leo Nnamdi Ozurumba-Dwight

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Messenger ribooxynucleic acid (mRNA) molecules are compositional, protein-based. These proteins, encoding mRNA molecules (which collectively connote the transcriptome), when analyzed by RNA sequencing (RNAseq), unveils the nature of gene expression in the RNA. The obtained gene expression provides clues of cellular traits and their dynamics in presentations. These can be studied in relation to function and responses. RNAseq is a practical concept in Genomics as it enables detection and quantitative analysis of mRNA molecules. Single cell and spatial transcriptomics both present varying avenues for expositions in genomic characteristics of single cells and pooled cells in disease conditions such as cancer, auto-immune diseases, hematopoietic based diseases, among others, from investigated biological tissue samples. Single cell transcriptomics helps conduct a direct assessment of each building unit of tissues (the cell) during diagnosis and molecular gene expressional studies. A typical technique to achieve this is through the use of a single-cell RNA sequencer (scRNAseq), which helps in conducting high throughput genomic expressional studies. However, this technique generates expressional gene data for several cells which lack presentations on the cells’ positional coordinates within the tissue. As science is developmental, the use of complimentary pre-established tissue reference maps using molecular and bioinformatics techniques has innovatively sprung-forth and is now used to resolve this set back to produce both levels of data in one shot of scRNAseq analysis. This is an emerging conceptual approach in methodology for integrative and progressively dependable transcriptomics analysis. This can support in-situ fashioned analysis for better understanding of tissue functional organization, unveil new biomarkers for early-stage detection of diseases, biomarkers for therapeutic targets in drug development, and exposit nature of cell-to-cell interactions. Also, these are vital genomic signatures and characterizations of clinical applications. Over the past decades, RNAseq has generated a wide array of information that is igniting bespoke breakthroughs and innovations in Biomedicine. On the other side, spatial transcriptomics is tissue level based and utilized to study biological specimens having heterogeneous features. It exposits the gross identity of investigated mammalian tissues, which can then be used to study cell differentiation, track cell line trajectory patterns and behavior, and regulatory homeostasis in disease states. Also, it requires referenced positional analysis to make up of genomic signatures that will be sassed from the single cells in the tissue sample. Given these two presented approaches to RNA transcriptomics study in varying quantities of cell lines, with avenues for appropriate resolutions, both approaches have made the study of gene expression from mRNA molecules interesting, progressive, developmental, and helping to tackle health challenges head-on.

Keywords: transcriptomics, RNA sequencing, single cell, spatial, gene expression.

Procedia PDF Downloads 103

Authors: Hasan Demiroğlu, Uğur Avcıbaşı, Serhan Sakarya, Perihan Ünak

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Implanted devices are progressively practiced in innovative medicine to relieve pain or improve a compromised function. Implant-associated infections represent an emerging complication, caused by organisms which adhere to the implant surface and grow embedded in a protective extracellular polymeric matrix, known as a biofilm. In addition, the microorganisms within biofilms enter a stationary growth phase and become phenotypically resistant to most antimicrobials, frequently causing treatment failure. In such cases, surgical removal of the implant is often required, causing high morbidity and substantial healthcare costs. Staphylococcus aureus is the most common pathogen causing implant-associated infections. Successful treatment of these infections includes early surgical intervention and antimicrobial treatment with bactericidal drugs that also act on the surface-adhering microorganisms. Linezolid is a promising anti-microbial with ant-staphylococcal activity, used for the treatment of MRSA infections. Linezolid is a synthetic antimicrobial and member of oxazolidinoni group, with a bacteriostatic or bactericidal dose-dependent antimicrobial mechanism against gram-positive bacteria. Intensive use of antibiotics, have emerged multi-resistant organisms over the years and major problems have begun to be experienced in the treatment of infections occurred with them. While new drugs have been developed worldwide, on the other hand infections formed with microorganisms which gained resistance against these drugs were reported and the scale of the problem increases gradually. Scientific studies about the production of bacterial biofilm increased in recent years. For this purpose, we investigated the activity of Lin, Lin radiolabeled with 131I (131I-Lin) and cold iodinated Lin (127I-Lin) against clinical strains of Staphylococcus aureus DSM 4910 in biofilm. In the first stage, radio and cold labeling studies were performed. Quality-control studies of Lin and iodo (radio and cold) Lin derivatives were carried out by using TLC (Thin Layer Radiochromatography) and HPLC (High Pressure Liquid Chromatography). In this context, it was found that the binding yield was obtained to be about 86±2 % for 131I-Lin. The minimal inhibitory concentration (MIC) of Lin, 127I-Lin and 131I-Lin for Staphylococcus aureus DSM 4910 strain were found to be 1µg/mL. In time-kill studies of Lin, 127I-Lin and 131I-Lin were producing ≥ 3 log10 decreases in viable counts (cfu/ml) within 6 h at 2 and 4 fold of MIC respectively. No viable bacteria were observed within the 24 h of the experiments. Biofilm eradication of S. aureus started with 64 µg/mL of Lin, 127I-Lin and 131I-Lin, and OD630 was 0.507±0.0.092, 0.589±0.058 and 0.266±0.047, respectively. The media control of biofilm producing Staphylococcus was 1.675±0,01 (OD630). 131I and 127I did not have any effects on biofilms. Lin and 127I-Lin were found less effectively than 131I-Lin at killing cells in biofilm and biofilm eradication. Our results demonstrate that the 131I-Lin have potent anti-biofilm activity against S. aureus compare to Lin, 127I-Lin and media control. This is suggested that, 131I may have harmful effect on biofilm structure.

Keywords: iodine-131, linezolid, radiolabeling, slime layer, Staphylococcus

Procedia PDF Downloads 538

Authors: Mengjiao Fan, Thomson W. L. Wong

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It is unavoidable that older adults may have to deal with aging-related motor problems. Aging is highly likely to affect motor learning and control as well. For example, older adults may suffer from poor motor function and quality of life due to age-related eye changes. These adverse changes in vision results in impairment of movement automaticity. Reaching is a fundamental component of various complex movements, which is therefore beneficial to explore the changes and adaptation in visuomotor behaviors. The current study aims to explore how aging affects visuomotor behaviors by comparing motor performance and gaze behaviors between two age groups (i.e., young and older adults). Visuomotor behaviors in reaching under providing or blocking online visual feedback (simulated visual deficiency) conditions were investigated in 60 healthy young adults (Mean age=24.49 years, SD=2.12) and 37 older adults (Mean age=70.07 years, SD=2.37) with normal or corrected-to-normal vision. Participants in each group were randomly allocated into two subgroups. Subgroup 1 was provided with online visual feedback of the hand-controlled mouse cursor. However, in subgroup 2, visual feedback was blocked to simulate visual deficiency. The experimental task required participants to complete 20 times of reaching to a target by controlling the mouse cursor on the computer screen. Among all the 20 trials, start position was upright in the center of the screen and target appeared at a randomly selected position by the tailor-made computer program. Primary outcomes of motor performance and gaze behaviours data were recorded by the EyeLink II (SR Research, Canada). The results suggested that aging seems to affect the performance of reaching tasks significantly in both visual feedback conditions. In both age groups, blocking online visual feedback of the cursor in reaching resulted in longer hand movement time (p < .001), longer reaching distance away from the target center (p<.001) and poorer reaching motor accuracy (p < .001). Concerning gaze behaviors, blocking online visual feedback increased the first fixation duration time in young adults (p<.001) but decreased it in older adults (p < .001). Besides, under the condition of providing online visual feedback of the cursor, older adults conducted a longer fixation dwell time on target throughout reaching than the young adults (p < .001) although the effect was not significant under blocking online visual feedback condition (p=.215). Therefore, the results suggested that different levels of visual feedback during movement execution can affect gaze behaviors differently in older and young adults. Differential effects by aging on visuomotor behaviors appear on two visual feedback patterns (i.e., blocking or providing online visual feedback of hand-controlled cursor in reaching). Several specific gaze behaviors among the older adults were found, which imply that blocking of visual feedback may act as a stimulus to seduce extra perceptive load in movement execution and age-related visual degeneration might further deteriorate the situation. It indeed provides us with insight for the future development of potential rehabilitative training method (e.g., well-designed errorless training) in enhancing visuomotor adaptation for our aging population in the context of improving their movement automaticity by facilitating their compensation of visual degeneration.

Keywords: aging effect, movement automaticity, reaching, visuomotor behaviors, visual degeneration

Procedia PDF Downloads 291

Authors: Saba Rahman, Arvind K. Jain, S. D. Bharti, T. K. Datta

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Chimneys are generally tall and slender structures with circular cross-sections, due to which they are highly prone to wind forces. Wind exerts pressure on the wall of the chimneys, which produces unwanted forces. Vortex-induced oscillation is one of such excitations which can lead to the failure of the chimneys. Therefore, vortex-induced oscillation of chimneys is of great concern to researchers and practitioners since many failures of chimneys due to vortex shedding have occurred in the past. As a consequence, extensive research has taken place on the subject over decades. Many laboratory experiments have been performed to verify the theoretical models proposed to predict vortex-induced forces, including aero-elastic effects. Comparatively, very few proto-type measurement data have been recorded to verify the proposed theoretical models. Because of this reason, the theoretical models developed with the help of experimental laboratory data are utilized for analyzing the chimneys for vortex-induced forces. This calls for reliability analysis of the predictions of the responses of the chimneys produced due to vortex shedding phenomena. Although several works of literature exist on the vortex-induced oscillation of chimneys, including code provisions, the reliability analysis of chimneys against failure caused due to vortex shedding is scanty. In the present study, the reliability analysis of chimneys against vortex shedding failure is presented, assuming the uncertainty in vortex shedding phenomena to be significantly more than other uncertainties, and hence, the latter is ignored. The vortex shedding is modeled as a stationary random process and is represented by a power spectral density function (PSDF). It is assumed that the vortex shedding forces are perfectly correlated and act over the top one-third height of the chimney. The PSDF of the tip displacement of the chimney is obtained by performing a frequency domain spectral analysis using a matrix approach. For this purpose, both chimney and random wind forces are discretized over a number of points along with the height of the chimney. The method of analysis duly accounts for the aero-elastic effects. The double barrier threshold crossing level, as proposed by Vanmarcke, is used for determining the probability of crossing different threshold levels of the tip displacement of the chimney. Assuming the annual distribution of the mean wind velocity to be a Gumbel type-I distribution, the fragility curve denoting the variation of the annual probability of threshold crossing against different threshold levels of the tip displacement of the chimney is determined. The reliability estimate is derived from the fragility curve. A 210m tall concrete chimney with a base diameter of 35m, top diameter as 21m, and thickness as 0.3m has been taken as an illustrative example. The terrain condition is assumed to be that corresponding to the city center. The expression for the PSDF of the vortex shedding force is taken to be used by Vickery and Basu. The results of the study show that the threshold crossing reliability of the tip displacement of the chimney is significantly influenced by the assumed structural damping and the Gumbel distribution parameters. Further, the aero-elastic effect influences the reliability estimate to a great extent for small structural damping.

Keywords: chimney, fragility curve, reliability analysis, vortex-induced vibration

Procedia PDF Downloads 137

Authors: Timur S. Zaripov, Artur K. Gilfanov, Sergei S. Sazhin, Steven M. Begg, Morgan R. Heikal

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The calculation of the concentration of inertial droplets in complex flows is encountered in the modelling of numerous engineering and environmental phenomena; for example, fuel droplets in internal combustion engines and airborne pollutant particles. The results of recent research, focused on the development of methods for calculating concentration and their implementation in the commercial CFD code, ANSYS Fluent, is presented here. The study is motivated by the investigation of the mixture preparation processes in internal combustion engines with direct injection of fuel sprays. Two methods are used in our analysis; the Fully Lagrangian method (also known as the Osiptsov method) and the Eulerian approach. The Osiptsov method predicts droplet concentrations along path lines by solving the equations for the components of the Jacobian of the Eulerian-Lagrangian transformation. This method significantly decreases the computational requirements as it does not require counting of large numbers of tracked droplets as in the case of the conventional Lagrangian approach. In the Eulerian approach the average droplet velocity is expressed as a function of the carrier phase velocity as an expansion over the droplet response time and transport equation can be solved in the Eulerian form. The advantage of the method is that droplet velocity can be found without solving additional partial differential equations for the droplet velocity field. The predictions from the two approaches were compared in the analysis of the problem of a dilute gas-droplet flow around an infinitely long, circular cylinder. The concentrations of inertial droplets, with Stokes numbers of 0.05, 0.1, 0.2, in steady-state and transient laminar flow conditions, were determined at various Reynolds numbers. In the steady-state case, flows with Reynolds numbers of 1, 10, and 100 were investigated. It has been shown that the results predicted using both methods are almost identical at small Reynolds and Stokes numbers. For larger values of these numbers (Stokes — 0.1, 0.2; Reynolds — 10, 100) the Eulerian approach predicted a wider spread in concentration in the perturbations caused by the cylinder that can be attributed to the averaged droplet velocity field. The transient droplet flow case was investigated for a Reynolds number of 200. Both methods predicted a high droplet concentration in the zones of high strain rate and low concentrations in zones of high vorticity. The maxima of droplet concentration predicted by the Osiptsov method was up to two orders of magnitude greater than that predicted by the Eulerian method; a significant variation for an approach widely used in engineering applications. Based on the results of these comparisons, the Osiptsov method has resulted in a more precise description of the local properties of the inertial droplet flow. The method has been applied to the analysis of the results of experimental observations of a liquid gasoline spray at representative fuel injection pressure conditions. The preliminary results show good qualitative agreement between the predictions of the model and experimental data.

Keywords: internal combustion engines, Eulerian approach, fully Lagrangian approach, gasoline fuel sprays, droplets and particle concentrations

Procedia PDF Downloads 235

Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

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Muscle represents about ¾ of the body mass, and a healthy muscular system is required for human performance. A healthy muscular system is dynamically balanced via the catabolic and anabolic process. High altitude associated hypoxia altered this redox balance via producing reactive oxygen and nitrogen species that ultimately modulates protein structure and function, hence, disrupts proteostasis or protein homeostasis. The mechanism by which proteostasis is clinched includes regulated protein translation, protein folding, and protein degradation machinery. Perturbation in any of these mechanisms could increase proteome imbalance in the cellular processes. Altered proteostasis in skeletal muscle is likely to be responsible for contributing muscular atrophy in response to hypoxia. Therefore, we planned to elucidate the mechanism involving altered proteostasis leading to skeletal muscle atrophy under chronic hypobaric hypoxia. Material and Methods-Male Sprague Dawley rats weighing about 200-220 were divided into five groups - Control (Normoxic animals), 1d, 3d, 7d and 14d hypobaric hypoxia exposed animals. The animals were exposed to simulated hypoxia equivalent to 282 torr pressure (equivalent to an altitude of 7620m, 8% oxygen) at 25°C. On completion of chronic hypobaric hypoxia (CHH) exposure, rats were sacrificed, muscle was excised and biochemical, histopathological and protein synthesis signaling were studied. Results-A number of changes were observed with the CHH exposure time period. ROS was increased significantly on 07 and 14 days which were attributed to protein oxidation via damaging muscle protein structure by oxidation of amino acids moiety. The oxidative damage to the protein further enhanced the various protein degradation pathways. Calcium activated cysteine proteases and other intracellular proteases participate in protein turnover in muscles. Therefore, we analysed calpain and 20S proteosome activity which were noticeably increased at CHH exposure as compared to control group representing enhanced muscle protein catabolism. Since inflammatory markers (myokines) affect protein synthesis and triggers degradation machinery. So, we determined inflammatory pathway regulated under hypoxic environment. Other striking finding of the study was upregulation of Akt/PKB translational machinery that was increased on CHH exposure. Akt, p-Akt, p70 S6kinase, and GSK- 3β expression were upregulated till 7d of CHH exposure. Apoptosis related markers, caspase-3, caspase-9 and annexin V was also increased on CHH exposure. Conclusion: The present study provides evidence of disrupted proteostasis under chronic hypobaric hypoxia. A profound loss of muscle mass is accompanied by the muscle damage leading to apoptosis and cell death under CHH. These cellular stress response pathways may play a pivotal role in hypobaric hypoxia induced skeletal muscle atrophy. Further research in these signaling pathways will lead to development of therapeutic interventions for amelioration of hypoxia induced muscle atrophy.

Keywords: Akt/PKB translational machinery, chronic hypobaric hypoxia, muscle atrophy, protein degradation

Procedia PDF Downloads 239

Authors: Ruairi J. McMillan

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Introduction: This critical analysis aims to ascertain how well neuroanatomical aetiologies are communicated within 20 case reports of aphasia. Neuroanatomical visualisations based on dissected brain specimens were produced and combined with white matter tract and vascular taxonomies of function in order to address the most consistently underreported features found within the aphasic case study reports. Together, these approaches are intended to integrate aphasiological knowledge from the past 20 years with aphasiological diagnostics, and to act as prototypal resources for both researchers and clinical professionals. The medico-legal precedent for aphasia diagnostics under Canadian, US and UK case law and the neuroimaging/neurological diagnostics relative to the functional capacity of aphasic patients are discussed in relation to the major findings of the literary analysis, neuroimaging protocols in clinical use today, and the neuroanatomical aetiologies of different aphasias. Basic Methodology: Literature searches of relevant scientific databases (e.g, OVID medline) were carried out using search terms such as aphasia case study (year) & stroke induced aphasia case study. A series of 7 diagnostic reporting criteria were formulated, and the resulting case studies were scored / 7 alongside clinical stroke criteria. In order to focus on the diagnostic assessment of the patient’s condition, only the case report proper (not the discussion) was used to quantify results. Statistical testing established if specific reporting criteria were associated with higher overall scores and potentially inferable increases in quality of reporting. Statistical testing of whether criteria scores were associated with an unclear/adjusted diagnosis were also tested, as well as the probability of a given criterion deviating from an expected estimate. Major Findings: The quantitative analysis of neuroanatomically driven diagnostics in case studies of aphasia revealed particularly low scores in the connection of neuroanatomical functions to aphasiological assessment (10%), and in the inclusion of white matter tracts within neuroimaging or assessment diagnostics (30%). Case studies which included clinical mention of white matter tracts within the report itself were distributed among higher scoring cases, as were case studies which (as clinically indicated) related the affected vascular region to the brain parenchyma of the language network. Concluding Statement: These findings indicate that certain neuroanatomical functions are integrated less often within the patient report than others, despite a precedent for well-integrated neuroanatomical aphasiology also being found among the case studies sampled, and despite these functions being clinically essential in diagnostic neuroimaging and aphasiological assessment. Therefore, ultimately the integration and specificity of aetiological neuroanatomy may contribute positively to the capacity and autonomy of aphasic patients as well as their clinicians. The integration of a full aetiological neuroanatomy within the reporting of aphasias may improve patient outcomes and sustain autonomy in the event of medico-ethical investigation.

Keywords: aphasia, language network, functional neuroanatomy, aphasiological diagnostics, medico-legal ethics

Procedia PDF Downloads 37

Authors: K. S. Poutanen, P. Dussort, A. Erkner, S. Fiszman, K. Karnik, M. Kristensen, C. F. M. Marsaux, S. Miquel-Kergoat, S. Pentikäinen, P. Putz, R. E. Steinert, J. Slavin, D. J. Mela

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Dietary fiber (DF) intake has been associated with lower body weight or less weight gain. These effects are generally attributed to putative effects of DF on appetite. Many intervention studies have tested the effect of DFs on appetite-related measures, with inconsistent results. However, DF includes a wide category of different compounds with diverse chemical and physical characteristics, and correspondingly diverse effects in human digestion. Thus, inconsistent results between DF consumption and appetite are not surprising. The specific contribution of different compounds with varying physico-chemical properties to appetite control and the mediating mechanisms are not well characterized. This systematic review aimed to assess the influence of specific DF characteristics, including viscosity, gel forming capacity, fermentability, and molecular weight, on appetite-related outcomes in healthy humans. Medline and FSTA databases were searched for controlled human intervention trials, testing the effects of well-characterized DFs on subjective satiety/appetite or energy intake outcomes. Studies were included only if they reported: 1) fiber name and origin, and 2) data on viscosity, gelling properties, fermentability, or molecular weight of the DF materials tested. The search generated 3001 unique records, 322 of which were selected for further consideration from title and abstract screening. Of these, 149 were excluded due to insufficient fiber characterization and 124 for other reasons (not original article, not randomized controlled trial, or no appetite related outcome), leaving 49 papers meeting all the inclusion criteria, most of which reported results from acute testing (<1 day). The eligible 49 papers described 90 comparisons of DFs in foods, beverages or supplements. DF-containing material of interest was efficacious for at least one appetite-related outcome in 51/90 comparisons. Gel-forming DF sources were most consistently efficacious but there were no clear associations between viscosity, MW or fermentability and appetite-related outcomes. A considerable number of papers had to be excluded from the review due to shortcomings in fiber characterization. To build understanding about the impact of DF on satiety/appetite specifically there should be clear hypotheses about the mechanisms behind the proposed beneficial effect of DF material on appetite, and sufficient data about the DF properties relevant for the hypothesized mechanisms to justify clinical testing. The hypothesized mechanisms should also guide the decision about relevant duration of exposure in studies, i.e. are the effects expected to occur during acute time frame (related to stomach emptying, digestion rate, etc.) or develop from sustained exposure (gut fermentation mediated mechanisms). More consistent measurement methods and reporting of fiber specifications and characterization are needed to establish reliable structure-function relationships for DF and health outcomes.

Keywords: appetite, dietary fiber, physico-chemical properties, satiety

Procedia PDF Downloads 206

Authors: Oibar Martinez, Clara Oliver, Jose Miguel Miranda

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In this paper, we discuss the standard improvements which can be made to reduce the earth resistance in difficult terrains for optimum lightning protection, what are the practical limitations, and how the modeling can be refined for accurate diagnostics and ground resistance minimization. Ground resistance minimization can be made via three different approaches: burying vertical electrodes connected in parallel, burying horizontal conductive plates or meshes, or modifying the own terrain, either by changing the entire terrain material in a large volume or by adding earth-enhancing compounds. The use of vertical electrodes connected in parallel pose several practical limitations. In order to prevent loss of effectiveness, it is necessary to keep a minimum distance between each electrode, which is typically around five times larger than the electrode length. Otherwise, the overlapping of the local equipotential lines around each electrode reduces the efficiency of the configuration. The addition of parallel electrodes reduces the resistance and facilitates the measurement, but the basic parallel resistor formula of circuit theory will always underestimate the final resistance. Numerical simulation of equipotential lines around the electrodes overcomes this limitation. The resistance of a single electrode will always be proportional to the soil resistivity. The electrodes are usually installed with a backfilling material of high conductivity, which increases the effective diameter. However, the improvement is marginal, since the electrode diameter counts in the estimation of the ground resistance via a logarithmic function. Substances that are used for efficient chemical treatment must be environmentally friendly and must feature stability, high hygroscopicity, low corrosivity, and high electrical conductivity. A number of earth enhancement materials are commercially available. Many are comprised of carbon-based materials or clays like bentonite. These materials can also be used as backfilling materials to reduce the resistance of an electrode. Chemical treatment of soil has environmental issues. Some products contain copper sulfate or other copper-based compounds, which may not be environmentally friendly. Carbon-based compounds are relatively inexpensive and they do have very low resistivities, but they also feature corrosion issues. Typically, the carbon can corrode and destroy a copper electrode in around five years. These compounds also have potential environmental concerns. Some earthing enhancement materials contain cement, which, after installation acquire properties that are very close to concrete. This prevents the earthing enhancement material from leaching into the soil. After analyzing different configurations, we conclude that a buried conductive ring with vertical electrodes connected periodically should be the optimum baseline solution for the grounding of a large size structure installed on a large resistivity terrain. In order to show this, a practical example is explained here where we simulate the ground resistance of a conductive ring buried in a terrain with a resistivity in the range of 1 kOhm·m.

Keywords: grounding improvements, large scale scientific instrument, lightning risk assessment, lightning standards

Procedia PDF Downloads 111

Authors: Marta Malo, Carlota Soto, Carmen García-Rosales, Teresa Hernández

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SiC based composites are candidates for possible use as structural and functional materials in the future fusion reactors, the main role is intended for the blanket modules. In the blanket, the neutrons produced in the fusion reaction slow down and their energy is transformed into heat in order to finally generate electrical power. In the blanket design named Dual Coolant Lead Lithium (DCLL), a PbLi alloy for power conversion and tritium breeding circulates inside hollow channels called Flow Channel Inserts (FCIs). These FCI must protect the steel structures against the highly corrosive PbLi liquid and the high temperatures, but also provide electrical insulation in order to minimize magnetohydrodynamic interactions of the flowing liquid metal with the high magnetic field present in a magnetically confined fusion environment. Due to their nominally high temperature and radiation stability as well as corrosion resistance, SiC is the main choice for the flow channel inserts. The significantly lower manufacturing cost presents porous SiC (dense coating is required in order to assure protection against corrosion and as a tritium barrier) as a firm alternative to SiC/SiC composites for this purpose. This application requires the materials to be exposed to high radiation levels and extreme temperatures, conditions for which previous studies have shown noticeable changes in both the microstructure and the electrical properties of different types of silicon carbide. Both initial properties and radiation/temperature induced damage strongly depend on the crystal structure, polytype, impurities/additives that are determined by the fabrication process, so the development of a suitable material requires full control of these variables. For this work, several SiC samples with different percentage of porosity and sintering additives have been manufactured by the so-called sacrificial template method at the Ceit-IK4 Technology Center (San Sebastián, Spain), and characterized at Ciemat (Madrid, Spain). Electrical conductivity was measured as a function of temperature before and after irradiation with 1.8 MeV electrons in the Ciemat HVEC Van de Graaff accelerator up to 140 MGy (~ 2·10 -5 dpa). Radiation-induced conductivity (RIC) was also examined during irradiation at 550 ºC for different dose rates (from 0.5 to 5 kGy/s). Although no significant RIC was found in general for any of the samples, electrical conductivity increase with irradiation dose was observed to occur for some compositions with a linear tendency. However, first results indicate enhanced radiation resistance for coated samples. Preliminary thermogravimetric tests of selected samples, together with posterior XRD analysis allowed interpret radiation-induced modification of the electrical conductivity in terms of changes in the SiC crystalline structure. Further analysis is needed in order to confirm this.

Keywords: DCLL blanket, electrical conductivity, flow channel insert, porous SiC, radiation damage, thermal stability

Procedia PDF Downloads 179

Authors: Subhash Nerella, Ziyuan Guan, Azra Bihorac, Parisa Rashidi

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Intensive care units (ICUs) provide care to critically ill patients in severe and life-threatening conditions. However, patient monitoring in the ICU is limited by the time and resource constraints imposed on healthcare providers. Many critical care indices such as mobility are still manually assessed, which can be subjective, prone to human errors, and lack granularity. Other important aspects, such as environmental factors, are not monitored at all. For example, critically ill patients often experience circadian disruptions due to the absence of effective environmental “timekeepers” such as the light/dark cycle and the systemic effect of acute illness on chronobiologic markers. Although the occurrence of delirium is associated with circadian disruption risk factors, these factors are not routinely monitored in the ICU. Hence, there is a critical unmet need to develop systems for precise and real-time assessment through novel enabling technologies. We have developed the mobility and circadian disruption quantification system (Mobi-DiQ) by augmenting biomarker and clinical data with pervasive sensing data to generate mobility and circadian cues related to mobility, nightly disruptions, and light and noise exposure. We hypothesize that Mobi-DiQ can provide accurate mobility and circadian cues that correlate with bedside clinical mobility assessments and circadian biomarkers, ultimately important for delirium risk assessment and prevention. The collected multimodal dataset consists of depth images, Electromyography (EMG) data, patient extremity movement captured by accelerometers, ambient light levels, Sound Pressure Level (SPL), and indoor air quality measured by volatile organic compounds, and the equivalent CO₂ concentration. For delirium risk assessment, the system recognizes mobility cues (axial body movement features and body key points) and circadian cues, including nightly disruptions, ambient SPL, and light intensity, as well as other environmental factors such as indoor air quality. The Mobi-DiQ system consists of three major components: the pervasive sensing system, a data storage and analysis server, and a data annotation system. For data collection, six local pervasive sensing systems were deployed, including a local computer and sensors. A video recording tool with graphical user interface (GUI) developed in python was used to capture depth image frames for analyzing patient mobility. All sensor data is encrypted, then automatically uploaded to the Mobi-DiQ server through a secured VPN connection. Several data pipelines are developed to automate the data transfer, curation, and data preparation for annotation and model training. The data curation and post-processing are performed on the server. A custom secure annotation tool with GUI was developed to annotate depth activity data. The annotation tool is linked to the MongoDB database to record the data annotation and to provide summarization. Docker containers are also utilized to manage services and pipelines running on the server in an isolated manner. The processed clinical data and annotations are used to train and develop real-time pervasive sensing systems to augment clinical decision-making and promote targeted interventions. In the future, we intend to evaluate our system as a clinical implementation trial, as well as to refine and validate it by using other data sources, including neurological data obtained through continuous electroencephalography (EEG).

Keywords: deep learning, delirium, healthcare, pervasive sensing

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Authors: Md. Samsuddin Ansari, Ashish Arora

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Every year 10 million people fall ill with one of the oldest diseases known as tuberculosis, caused by Mycobacterium tuberculosis. The success of M. tuberculosis as a pathogen is because of its ability to persist in host tissues. Multidrug resistance (MDR) mycobacteria cases increase every day, which is associated with efflux pumps controlled at the level of transcription. The transcription regulators of MDR transporters in bacteria belong to one of the following four regulatory protein families: AraC, MarR, MerR, and TetR. Phenolic acid decarboxylase repressor (PadR), like a family of transcription regulators, is closely related to the MarR family. Phenolic acid decarboxylase repressor (PadR) was first identified as a transcription factor involved in the regulation of phenolic acid stress response in various microorganisms (including Mycobacterium tuberculosis H37Rv). Recently research has shown that the PadR family transcription factors are global, multifunction transcription regulators. Rv0047c is a PadR subfamily-1 protein. We are exploring the biophysical and structural characterization of Rv0047c. The Rv0047 gene was amplified by PCR using the primers containing EcoRI and HindIII restriction enzyme sites cloned in pET-NH6 vector and overexpressed in DH5α and BL21 (λDE3) cells of E. coli following purification with Ni2+-NTA column and size exclusion chromatography. We did DSC to know the thermal stability; the Tm (transition temperature) of protein is 55.29ºC, and ΔH (enthalpy change) of 6.92 kcal/mol. Circular dichroism to know the secondary structure and conformation and fluorescence spectroscopy for tertiary structure study of protein. To understand the effect of pH on the structure, function, and stability of Rv0047c we employed spectroscopy techniques such as circular dichroism, fluorescence, and absorbance measurements in a wide range of pH (from pH-2.0 to pH-12). At low and high pH, it shows drastic changes in the secondary and tertiary structure of the protein. EMSA studies showed the specific binding of Rv0047c with its own 30-bp promoter region. To determine the effect of complex formation on the secondary structure of Rv0047c, we examined the CD spectra of the complex of Rv0047c with promoter DNA of rv0047. The functional role of Rv0047c was characterized by over-expressing the Rv0047c gene under the control of hsp60 promoter in Mycobacterium tuberculosis H37Rv. We have predicted the three-dimensional structure of Rv0047c using the Swiss Model and Modeller, with validity checked by the Ramachandra plot. We did molecular docking of Rv0047c with dnaA, through PatchDock following refinement through FireDock. Through this, it is possible to easily identify the binding hot-stop of the receptor molecule with that of the ligand, the nature of the interface itself, and the conformational change undergone by the protein pattern. We are using X-crystallography to unravel the structure of Rv0047c. Overall the studies show that Rv0047c may have transcription regulation along with providing an insight into the activity of Rv0047c in the pH range of subcellular environment and helps to understand the protein-protein interaction, a novel target to kill dormant bacteria and potential strategy for tuberculosis control.

Keywords: mycobacterium tuberculosis, phenolic acid decarboxylase repressor, Rv0047c, Circular dichroism, fluorescence spectroscopy, docking, protein-protein interaction

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Authors: Maria Corazon Tapang-Lopez, Alyn Joy Dela Cruz Baltazar, Bobby Jones Villanueva Domdom

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The requisite for an organization implementing quality management system to sustain its compliance to the requirements and commitment for continuous improvement is even higher. It is expected that the offices and units has high and consistent compliance to the established processes and procedures. The Development Academy of the Philippines has been operating under project management to which is has a quality management certification. To further realize its mandate as a think-tank and capacity builder of the government, DAP expanded its operation and started to grant graduate degree through its Graduate School of Public and Development Management (GSPDM). As the academic arm of the Academy, GSPDM offers graduate degree programs on public management and productivity & quality aligned to the institutional trusts. For a time, the documented procedures and processes of a project management seem to fit the Graduate School. However, there has been a significant growth in the operations of the GSPDM in terms of the graduate programs offered that directly increase the number of students. There is an apparent necessity to align the project management system into a more educational system otherwise it will no longer be responsive to the development that are taking place. The strongly advocate and encourage its students to pursue internal and external improvement to cope up with the challenges of providing quality service to their own clients and to our country. If innovation will not take roots in the grounds of GSPDM, then how will it serve the purpose of “walking the talk”? This research was conducted to assess the diverse flow of the existing internal operations and processes of the DAP’s project management and GSPDM’s school management that will serve as basis to develop a system that will harmonize into one, the Learning Management System. The study documented the existing process of GSPDM following the project management phases of conceptualization & development, negotiation & contracting, mobilization, implementation, and closure into different flow charts of the key activities. The primary source of information as respondents were the different groups involved into the delivery of graduate programs - the executive, learning management team and administrative support offices. The Learning Management System (LMS) shall capture the unique and critical processes of the GSPDM as a degree-granting unit of the Academy. The LMS is the harmonized project management and school management system that shall serve as the standard system and procedure for all the programs within the GSPDM. The unique processes cover the three important areas of school management – student, curriculum, and faculty. The required processes of these main areas such as enrolment, course syllabus development, and faculty evaluation were appropriately placed within the phases of the project management system. Further, the research shall identify critical reports and generate manageable documents and records to ensure accuracy, consistency and reliable information. The researchers had an in-depth review of the DAP-GSDPM’s mandate, analyze the various documents, and conducted series of focused group discussions. A comprehensive review on flow chart system prior and various models of school management systems were made. Subsequently, the final output of the research is a work instructions manual that will be presented to the Academy’s Quality Management Council and eventually an additional scope for ISO certification. The manual shall include documented forms, iterative flow charts and program Gantt chart that will have a parallel development of automated systems.

Keywords: productivity, quality, learning management system, agency-based graduate school

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Authors: Vanita Singh

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In developing countries, there are conflicting political agendas; policy makers have to prioritize issues from a list of issues competing for the limited resources. Thus, it is imperative to understand how some issues gain attention, and others lose in the policy circles. Multiple-Streams Theory of Kingdon (1984) is among the influential theories that help to understand the public policy process and is utilitarian for health policy makers to understand how certain health issues emerge on the policy agendas. The issue of maternal mortality was long standing in India and was linked with high birth rate thus the focus of maternal health policy was on family planning since India’s independence. However, a paradigm shift was noted in the maternal health policy in the year 1992 with the launch of Safe Motherhood Programme and then in the year 2005, when the agenda of maternal health policy became universalizing institutional deliveries and phasing-out of Traditional Birth Attendants (TBAs) from the health system. There were many solutions proposed by policy communities other than universalizing of institutional deliveries, including training of TBAs and improving socio-economic conditions of pregnant women. However, Government of India favored medical community, which was advocating for the policy of universalizing institutional delivery, and neglected the solutions proposed by other policy communities. It took almost 15 years for the advocates of institutional delivery to transform their proposed solution into a program - the Janani Suraksha Yojana (JSY), a safe-motherhood program promoting institutional delivery through cash incentives to pregnant women. Thus, the case of safe motherhood policy in India is worth studying to understand how certain issues/problems gain political attention and how advocacy work in policy circles. This paper attempts to understand the factors that favored the agenda of safe-motherhood in the policy circle in India, using John Kingdon’s Multiple-Stream model of agenda-setting. Through document analysis and literature review, the paper traces the evolution of safe motherhood program and maternal health policy. The study has used open source documents available on the website of Ministry of Health and Family Welfare, media reports (Times of India Archive) and related research papers. The documents analyzed include National health policy-1983, National Health Policy-2002, written reports of Ministry of Health and Family Welfare Department, National Rural Health Mission (NRHM) document, documents related to Janani Suraksha Yojana and research articles related to maternal health programme in India. The study finds that focusing events and credible indicators coupled with media attention has the potential to recognize a problem. The political elites favor clearly defined and well-accepted solutions. The trans-national organizations affect the agenda-setting process in a country through conditional resource provision. The closely-knit policy communities and political entrepreneurship are required for advocating solutions high on agendas. The study has implications for health policy makers in identifying factors that have the potential to affect the agenda-setting process for a desired policy agenda and identify the challenges in generating political priorities.

Keywords: agenda-setting, focusing events, Kingdon’s model, safe motherhood program India

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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Authors: Gyu-Dong Kim, Wuk-Jae Yoo, Sang-Youl Lee

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Composite structures offer numerous advantages over conventional structural systems in the form of higher specific stiffness and strength, lower life-cycle costs, and benefits such as easy installation and improved safety. Recently, there has been a considerable increase in the use of composites in engineering applications and as wraps for seismic upgrading and repairs. However, these composites deteriorate with time because of outdated materials, excessive use, repetitive loading, climatic conditions, manufacturing errors, and deficiencies in inspection methods. In particular, damaged fibers in a composite result in significant degradation of structural performance. In order to reduce the failure probability of composites in service, techniques to assess the condition of the composites to prevent continual growth of fiber damage are required. Condition assessment technology and nondestructive evaluation (NDE) techniques have provided various solutions for the safety of structures by means of detecting damage or defects from static or dynamic responses induced by external loading. A variety of techniques based on detecting the changes in static or dynamic behavior of isotropic structures has been developed in the last two decades. These methods, based on analytical approaches, are limited in their capabilities in dealing with complex systems, primarily because of their limitations in handling different loading and boundary conditions. Recently, investigators have introduced direct search methods based on metaheuristics techniques and artificial intelligence, such as genetic algorithms (GA), simulated annealing (SA) methods, and neural networks (NN), and have promisingly applied these methods to the field of structural identification. Among them, GAs attract our attention because they do not require a considerable amount of data in advance in dealing with complex problems and can make a global solution search possible as opposed to classical gradient-based optimization techniques. In this study, we propose an alternative damage-detection technique that can determine the degraded stiffness distribution of vibrating laminated composites made of Glass Fiber-reinforced Polymer (GFRP). The proposed method uses a modified form of the bivariate Gaussian distribution function to detect degraded stiffness characteristics. In addition, this study presents a method to detect the fiber property variation of laminated composite plates from the micromechanical point of view. The finite element model is used to study free vibrations of laminated composite plates for fiber stiffness degradation. In order to solve the inverse problem using the combined method, this study uses only first mode shapes in a structure for the measured frequency data. In particular, this study focuses on the effect of the interaction among various parameters, such as fiber angles, layup sequences, and damage distributions, on fiber-stiffness damage detection.

Keywords: stiffness detection, fiber damage, genetic algorithm, layup sequences

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Authors: Pedro Llanos, Diego García

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This paper is addressed to expanding our understanding of the effects of hypoxia training on our bodies to better model its dynamics and leverage some of its implications and effects on human health. Hypoxia training is a recommended practice for military and civilian pilots that allow them to recognize their early hypoxia signs and symptoms, and Scientist Astronaut Candidates (SACs) who underwent hypobaric hypoxia (HH) exposure as part of a training activity for prospective suborbital flight applications. This observational-analytical study describes physiologic responses and symptoms experienced by a SAC group before, during and after HH exposure and proposes a model for assessing predicted versus observed physiological responses. A group of individuals with diverse Science Technology Engineering Mathematics (STEM) backgrounds conducted a hypobaric training session to an altitude up to 22,000 ft (FL220) or 6,705 meters, where heart rate (HR), breathing rate (BR) and core temperature (Tc) were monitored with the use of a chest strap sensor pre and post HH exposure. A pulse oximeter registered levels of saturation of oxygen (SpO₂), number and duration of desaturations during the HH chamber flight. Hypoxia symptoms as described by the SACs during the HH training session were also registered. This data allowed to generate a preliminary predictive model of the oxygen desaturation and O₂ pressure curve for each subject, which consists of a sixth-order polynomial fit during exposure, and a fifth or fourth-order polynomial fit during recovery. Data analysis showed that HR and BR showed no significant differences between pre and post HH exposure in most of the SACs, while Tc measures showed slight but consistent decrement changes. All subjects registered SpO₂ greater than 94% for the majority of their individual HH exposures, but all of them presented at least one clinically significant desaturation (SpO₂ < 85% for more than 5 seconds) and half of the individuals showed SpO₂ below 87% for at least 30% of their HH exposure time. Finally, real time collection of HH symptoms presented temperature somatosensory perceptions (SP) for 65% of individuals, and task-focus issues for 52.5% of individuals as the most common HH indications. 95% of the subjects experienced HH onset symptoms below FL180; all participants achieved full recovery of HH symptoms within 1 minute of donning their O₂ mask. The current HH study performed on this group of individuals suggests a rapid and fully reversible physiologic response after HH exposure as expected and obtained in previous studies. Our data showed consistent results between predicted versus observed SpO₂ curves during HH suggesting a mathematical function that may be used to model HH performance deficiencies. During the HH study, real-time HH symptoms were registered providing evidenced SP and task focusing as the earliest and most common indicators. Finally, an assessment of HH signs of symptoms in a group of heterogeneous, non-pilot individuals showed similar results to previous studies in homogeneous populations of pilots.

Keywords: slow onset hypoxia, hypobaric chamber training, altitude sickness, symptoms and altitude, pressure cabin

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Authors: Nataliya G. Olkhovik

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Nowadays in the system of Russian higher medical education there have been undertaken initiatives that resulted in focusing on the resources of e-learning in teaching foreign languages. Obviously, the face-to-face communication in foreign languages bears much more advantages in terms of effectiveness in comparison with the potential of e-learning. Thus, we’ve faced the necessity of strengthening the capacity of e-learning via integration of active methods into the process of teaching foreign languages, such as project activity of students. Successful project activity of students should involve the following components: monitoring, control, methods of organizing the student’s activity in foreign languages, stimulating their interest in the chosen project, approaches to self-assessment and methods of raising their self-esteem. The contemporary methodology assumes the project as a specific method, which activates potential of a student’s cognitive function, emotional reaction, ability to work in the team, commitment, skills of cooperation and, consequently, their readiness to verbalize ideas, thoughts and attitudes. Verbal activity in the foreign language is a complex conception that consolidates both cognitive (involving speech) capacity and individual traits and attitudes such as initiative, empathy, devotion, responsibility etc. Once we organize the project activity by the means of e-learning within the ‘Foreign language’ discipline we have to take into consideration all mentioned above characteristics and work out an effective way to implement it into the teaching practice to boost its educational potential. We have integrated into the e-platform Moodle the module of project activity consisting of the following blocks of tasks that lead students to research, cooperate, strive to leadership, chase the goal and finally verbalize their intentions. Firstly, we introduce the project through activating self-activity of students by the tasks of the phase ‘Preparation of the project’: choose the topic and justify it; find out the problematic situation and its components; set the goals; create your team, choose the leader, distribute the roles in your team; make a written report on grounding the validity of your choices. Secondly, in the ‘Planning the project’ phase we ask students to represent the analysis of the problem in terms of reasons, ways and methods of solution and define the structure of their project (here students may choose oral or written presentation by drawing up the claim in the e-platform about their wish, whereas the teacher decides what form of presentation to prefer). Thirdly, the students have to design the visual aids, speech samples (functional phrases, introductory words, keywords, synonyms, opposites, attributive constructions) and then after checking, discussing and correcting with a teacher via the means of Moodle present it in front of the audience. And finally, we introduce the phase of self-reflection that aims to awake the inner desire of students to improve their verbal activity in a foreign language. As a result, by implementing the project activity into the e-platform and project activity, we try to widen the frameworks of a traditional lesson of foreign languages through tapping the potential of personal traits and attitudes of students.

Keywords: active methods, e-learning, improving verbal activity in foreign languages, personal traits and attitudes

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Authors: Mariana Stuparu-Cretu, Doina-Carina Voinescu, Rodica-Mihaela Dinica, Daniela Borda, Camelia Vizireanu, Gabriela Iordachescu, Camelia Busila

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Obesity is involved in the etiology or acceleration of progression of important non-communicable diseases, such as: metabolic, cardiovascular, rheumatological, oncological and depression. It is a need to prevent the obesity occurrence, like a key link in disease management. From this point of view, the best approach is to early educate youngsters upon the need for a healthy nutrition lifestyle associated with constant physical activities. The objective of the study was to assess correlations between weight condition, physical activities and food preferences of students from South East Romania. Questionnaires were applied on high school students in Galati: 1006 girls and 880 boys, aged between 14 and 19 years (being approved by Local School Inspectorate and the Ethics Committee of the 'Dunarea de Jos' University of Galati). The collected answers have been statistically processed by using the multivariate regression method (PLS2) by Unscramble X program (Camo, Norway). Multiple variables such as age group, body mass index, nutritional habits and physical activities were separately analysed, depending on gender and general mathematical models were proposed to explain the obesity trend at an early age. The study results show that overweight and obesity are present in less than a fifth of the adolescents who were surveyed. With a very small variation and a strong correlation of over 86% for 99% of the cases, a general preference for sweet foods, nocturnal eating associated with computer work and a reduced period of physical activity is noticed for girls. In addition, the overweight girls consume sweet juices and alcohol, although a percentage of them also practice the gym. There is also a percentage of the normoponderal girls that consume high caloric foods which predispose this group to turn into overweight cases in time. Within the studied group, statistics for the boys show a positive correlation of almost 87% for over 96% of cases. They prefer high calories foods, fast food, and sweet juices, and perform medium physical activities. Both overweight and underweight boys are more sedentary. Over 15% of girls and over a quarter of boys consume alcohol. All these bad eating habits seem to increase with age, for both sexes. To conclude, obesity and overweight assessed in adolescents in S-E Romania reveal nonsignificant percentage differences between boys and girls. However, young people in this area of the country are sedentary in general; a significant percentage prefers sweets / sweet juices / fast-food and practice computer nourishing. The authors consider that at this age, it is very useful to adapt nutritional education by new methods of food processing and market supply. This would require an early understanding of the difference among foods and nutrients and the benefits of physical activities integrated into the healthy current lifestyle, as a measure for preventing and managing non-communicable chronic diseases related to nutritional errors and sedentarism. Acknowledgment— This study has been partial founded by the Francophone University Agency, Project Réseau régional dans le domaine de la santé, la nutrition et la sécurité alimentaire (SaIN), no.21899/ 06.09.2017.

Keywords: adolescents, body mass index, nutritional habits, obesity, physical activity

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Authors: Yael Livneh, Shay Tzafrir, Ilan Meshoulam

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Technological startup companies have been recognized as bearing tremendous potential for business and economic success. However, many entrepreneurs who produce promising innovative ideas fail to implement them as successful businesses. A key argument for such failure is the entrepreneurs' lack of competence in adaptation of the relevant level of formality of human resource management (HRM). The purpose of the present research was to examine multiple antecedents and consequences of HRM formality in growing startup companies. A review of the research literature identified two central components of HRM formality: HR control and professionalism. The effect of three contextual predictors was examined. The first was an intra-organizational factor: the development level of the organization. We based on a differentiation between knowledge exploration and knowledge exploitation. At a given time, the organization chooses to focus on a specific mix of these orientations, a choice which requires an appropriate level of HRM formality, in order to efficiently overcome the challenges. It was hypothesized that the mix of orientations of knowledge exploration and knowledge exploitation would predict HRM formality. The second predictor was the personal characteristics the organization's leader. According the idea of blueprint effect of CEO's on HRM, it was hypothesized that the CEO's cognitive style would predict HRM formality. The third contextual predictor was an external organizational factor: the level of investor involvement. By using the agency theory, and based on Transaction Cost Economy, it was hypothesized that the level of investor involvement in general management and HRM would be positively related to the HRM formality. The effect of formality on trust was examined directly and indirectly by the mediation role of procedural justice. The research method included a time-lagged field study. In the first study, data was obtained using three questionnaires, each directed to a different source: CEO, HR position-holder and employees. 43 companies participated in this study. The second study was conducted approximately a year later. Data was recollected using three questionnaires by reapplying the same sample. 41 companies participated in the second study. The organizations samples included technological startup companies. Both studies included 884 respondents. The results indicated consistency between the two studies. HRM formality was predicted by the intra-organizational factor as well as the personal characteristics of the CEO, but not at all by the external organizational context. Specifically, the organizational orientations was the greatest contributor to both components of HRM formality. The cognitive style predicted formality to a lesser extent. The investor's involvement was found not to have any predictive effect on the HRM formality. The results indicated a positive contribution to trust in HRM, mainly via the mediation of procedural justice. This study contributed a new concept for technological startup company development by a mixture of organizational orientation. Practical implications indicated that the level of HRM formality should be matched to that of the company's development. This match should be challenged and adjusted periodically by referring to the organization orientation, relevant HR practices, and HR function characteristics. A relevant matching could enhance further trust and business success.

Keywords: control, formality, human resource management, organizational development, professionalism, technological startup company

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Authors: Márcia Afonso, Cristina Fael, Marisa Dinis-Almeida

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Population growth in cities has led to an increase in the infrastructures construction, including buildings and roadways. This aspect leads directly to the soils waterproofing. In turn, changes in precipitation patterns are developing into higher and more frequent intensities. Thus, these two conjugated aspects decrease the rainwater infiltration into soils and increase the volume of surface runoff. The practice of green and sustainable urban solutions has encouraged research in these areas. The porous asphalt pavement, as a green infrastructure, is part of practical solutions set to address urban challenges related to land use and adaptation to climate change. In this field, permeable pavements with porous asphalt mixtures (PA) have several advantages in terms of reducing the runoff generated by the floods. The porous structure of these pavements, compared to a conventional asphalt pavement, allows the rainwater infiltration in the subsoil, and consequently, the water quality improvement. This green infrastructure solution can be applied in cities, particularly in streets or parking lots to mitigate the floods effects. Over the years, the pores of these pavements can be filled by sediment, reducing their function in the rainwater infiltration. Thus, double layer porous asphalt (DLPA) was developed to mitigate the clogging effect and facilitate the water infiltration into the lower layers. This study intends to deepen the knowledge of the performance of DLPA when subjected to clogging. The experimental methodology consisted on four evaluation phases of the DLPA infiltration capacity submitted to three precipitation events (100, 200 and 300 mm/h) in each phase. The evaluation first phase determined the behavior after DLPA construction. In phases two and three, two 500 g/m² clogging cycles were performed, totaling a 1000 g/m² final simulation. Sand with gradation accented in fine particles was used as clogging material. In the last phase, the DLPA was subjected to simple sweeping and vacuuming maintenance. A precipitation simulator, type sprinkler, capable of simulating the real precipitation was developed for this purpose. The main conclusions show that the DLPA has the capacity to drain the water, even after two clogging cycles. The infiltration results of flows lead to an efficient performance of the DPLA in the surface runoff attenuation, since this was not observed in any of the evaluation phases, even at intensities of 200 and 300 mm/h, simulating intense precipitation events. The infiltration capacity under clogging conditions decreased about 7% on average in the three intensities relative to the initial performance that is after construction. However, this was restored when subjected to simple maintenance, recovering the DLPA hydraulic functionality. In summary, the study proved the efficacy of using a DLPA when it retains thicker surface sediments and limits the fine sediments entry to the remaining layers. At the same time, it is guaranteed the rainwater infiltration and the surface runoff reduction and is therefore a viable solution to put into practice in permeable pavements.

Keywords: clogging, double layer porous asphalt, infiltration capacity, rainfall intensity

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Authors: Alena Kulikova, Leonid Parmaksiz, Ekaterina Orel

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Social and emotional skills are considered by modern researchers as predictors of a person's success both in specific areas of activity and in the life of a person as a whole. The popularity of this scientific direction ensures the emergence of a large number of practices aimed at developing and evaluating socio-emotional skills. Assessment of social and emotional development is carried out at the national level, as well as at the level of individual regions and institutions. Despite the fact that many of the already existing social and emotional skills assessment tools are quite convenient and reliable, there are now more and more new technologies and task formats which improve the basic characteristics of the tools. Thus, the goal of the current study is to develop a tool for assessing social and emotional skills such as emotion recognition, emotion regulation, empathy and a culture of self-care. To develop a tool assessing social and emotional skills, Rasch-Gutman scenario-based approach was used. This approach has shown its reliability and merit for measuring various complex constructs: parental involvement; teacher practices that support cultural diversity and equity; willingness to participate in the life of the community after psychiatric rehabilitation; educational motivation and others. To assess emotion recognition, we used a situational judgment task based on OCC (Ortony, Clore, and Collins) emotions theory. The main advantage of these two approaches compare to classical Likert scales is that it reduces social desirability in answers. A field test to check the psychometric properties of the developed instrument was conducted. The instrument was developed for the presidential autonomous non-profit organization “Russia - Land of Opportunity” for nationwide soft skills assessment among higher education students. The sample for the field test consisted of 500 people, students aged from 18 to 25 (mean = 20; standard deviation 1.8), 71% female. 67% of students are only studying and are not currently working and 500 employed adults aged from 26 to 65 (mean = 42.5; SD 9), 57% female. Analysis of the psychometric characteristics of the scales was carried out using the methods of IRT (Item Response Theory). A one-parameter rating scale model RSM (Rating scale model) and Graded Response model (GRM) of the modern testing theory were applied. GRM is a polyatomic extension of the dichotomous two-parameter model of modern testing theory (2PL) based on the cumulative logit function for modeling the probability of a correct answer. The validity of the developed scales was assessed using correlation analysis and MTMM (multitrait-multimethod matrix). The developed instrument showed good psychometric quality and can be used by HR specialists or educational management. The detailed results of a psychometric study of the quality of the instrument, including the functioning of the tasks of each scale, will be presented. Also, the results of the validity study by MTMM analysis will be discussed.

Keywords: social and emotional skills, psychometrics, MTMM, IRT

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Authors: Merve Begum Terzi, Orhan Arikan, Adnan Abaci, Mustafa Candemir

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Acute myocardial infarction is a major cause of death in the world. Therefore, its fast and reliable diagnosis is a major clinical need. ECG is the most important diagnostic methodology which is used to make decisions about the management of the cardiovascular diseases. In patients with acute myocardial ischemia, temporary chest pains together with changes in ST segment and T wave of ECG occur shortly before the start of myocardial infarction. In this study, a technique which detects changes in ST/T sections of ECG is developed for the early diagnosis of acute myocardial ischemia. For this purpose, a database of real ECG recordings that contains a set of records from 75 patients presenting symptoms of chest pain who underwent elective percutaneous coronary intervention (PCI) is constituted. 12-lead ECG’s of the patients were recorded before and during the PCI procedure. Two ECG epochs, which are the pre-inflation ECG which is acquired before any catheter insertion and the occlusion ECG which is acquired during balloon inflation, are analyzed for each patient. By using pre-inflation and occlusion recordings, ECG features that are critical in the detection of acute myocardial ischemia are identified and the most discriminative features for the detection of acute myocardial ischemia are extracted. A classification technique based on support vector machine (SVM) approach operating with linear and radial basis function (RBF) kernels to detect ischemic events by using ST-T derived joint features from non-ischemic and ischemic states of the patients is developed. The dataset is randomly divided into training and testing sets and the training set is used to optimize SVM hyperparameters by using grid-search method and 10fold cross-validation. SVMs are designed specifically for each patient by tuning the kernel parameters in order to obtain the optimal classification performance results. As a result of implementing the developed classification technique to real ECG recordings, it is shown that the proposed technique provides highly reliable detections of the anomalies in ECG signals. Furthermore, to develop a detection technique that can be used in the absence of ECG recording obtained during healthy stage, the detection of acute myocardial ischemia based on ECG recordings of the patients obtained during ischemia is also investigated. For this purpose, a Gaussian mixture model (GMM) is used to represent the joint pdf of the most discriminating ECG features of myocardial ischemia. Then, a Neyman-Pearson type of approach is developed to provide detection of outliers that would correspond to acute myocardial ischemia. Neyman – Pearson decision strategy is used by computing the average log likelihood values of ECG segments and comparing them with a range of different threshold values. For different discrimination threshold values and number of ECG segments, probability of detection and probability of false alarm values are computed, and the corresponding ROC curves are obtained. The results indicate that increasing number of ECG segments provide higher performance for GMM based classification. Moreover, the comparison between the performances of SVM and GMM based classification showed that SVM provides higher classification performance results over ECG recordings of considerable number of patients.

Keywords: ECG classification, Gaussian mixture model, Neyman–Pearson approach, support vector machine

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Authors: Silvia Baralla, Raffaella Zucaro, Romina Lorenzetti

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Water management needs to cope with economic, societal, and environmental changes. This could be guaranteed through 'shifting from government to governance'. In the last decades, it was applied in Europe through and within important legislative pillars (Water Framework Directive and Common Agricultural Policy) and their measures focused on resilience and adaptation to climate change, with particular attention to the creation of synergies among policies and all the actors involved at different levels. Within the climate change context, the agricultural sector can play, through sustainable water management, a leading role for climate-resilient growth and environmental integrity. A recent analysis on the water management governance of different countries identified some common gaps dealing with administrative, policy, information, capacity building, funding, objective, and accountability. The ability of a country to fill these gaps is an essential requirement to make some of the changes requested by Europe, in particular the improvement of the agro-ecosystem resilience to the effect of climatic change, supporting green and digital transitions, and sustainable water use. This research aims to contribute in sharing examples of water governances and related advantages useful to fill the highlighted gaps. Italy has developed a strong and exhaustive model of water governance in order to react with strategic and synergic actions since it is one of the European countries most threatened by climate change and its extreme events (drought, floods). In particular, the Italian water governance model was able to overcome several gaps, specifically as concerns the water use in agriculture, adopting strategies as a systemic/integrated approach, the stakeholder engagement, capacity building, the improvement of planning and monitoring ability, and an adaptive/resilient strategy for funding activities. They were carried out, putting in place regulatory, structural, and management actions. Regulatory actions include both the institution of technical committees grouping together water decision-makers and the elaboration of operative manuals and guidelines by means of a participative and cross-cutting approach. Structural actions deal with the funding of interventions within European and national funds according to the principles of coherence and complementarity. Finally, management actions regard the introduction of operational tools to support decision-makers in order to improve planning and monitoring ability. In particular, two cross-functional and interoperable web databases were introduced: SIGRIAN (National Information System for Water Resources Management in Agriculture) and DANIA (National Database of Investments for Irrigation and the Environment). Their interconnection allows to support sustainable investments, taking into account the compliance about irrigation volumes quantified in SIGRIAN, ensuring a high level of attention on water saving, and monitoring the efficiency of funding. Main positive results from the Italian water governance model deal with a synergic and coordinated work at the national, regional, and local level among institutions, the transparency on water use in agriculture, a deeper understanding from the stakeholder side of the importance of their roles and of their own potential benefits and the capacity to guarantee continuity to this model, through a sensitization process and the combined use of management operational tools.

Keywords: agricultural sustainability, governance model, water management, water policies

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Authors: Kriti Jain, Sucha Singh Gill

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Subsidies have been a major part of agricultural policies around the world, and more extensively since the green revolution in developing countries, for the sake of attaining higher agricultural productivity and achieving food security. But entrenched subsidies lead to distorted incentives and promote inefficiencies in the agricultural sector, threatening the viability of these very subsidies and sustainability of the agricultural production systems, posing a threat to the livelihood of farmers and laborers dependent on it. This paper analyzes the economic and ecological sustainability implications of prolonged input and output subsidies in agriculture by studying the case of Indian Punjab, an agriculturally developed state responsible for ensuring food security in the country when it was facing a major food crisis. The paper focuses specifically on the environmentally unsustainable cropping pattern changes as a result of Minimum Support Price (MSP) and assured procurement and on the resource use efficiency and cost implications of power subsidy for irrigation in Punjab. The study is based on an analysis of both secondary and primary data sources. Using secondary data, a time series analysis was done to capture the changes in Punjab’s cropping pattern, water table depth, fertilizer consumption, and electrification of agriculture. This has been done to examine the role of price and output support adopted to encourage the adoption of green revolution technology in changing the cropping structure of the state, resulting in increased input use intensities (especially groundwater and fertilizers), which harms the ecological balance and decreases factor productivity. Evaluation of electrification of Punjab agriculture helped evaluate the trend in electricity productivity of agriculture and how free power imposed further pressure on the extant agricultural ecosystem. Using data collected from a primary survey of 320 farmers in Punjab, the extent of wasteful application of groundwater irrigation, water productivity of output, electricity usage, and cost of irrigation driven electricity subsidy to the exchequer were estimated for the dominant cropping pattern amongst farmers. The main findings of the study revealed how because of a subsidy has driven agricultural framework, Punjab has lost area under agro climatically suitable and staple crops and moved towards a paddy-wheat cropping system, that is gnawing away the state’s natural resources like water table has been declining at a significant rate of 25 cms per year since 1975-76, and excessive and imbalanced fertilizer usage has led to declining soil fertility in the state. With electricity-driven tubewells as the major source of irrigation within a regime of free electricity and water-intensive crop cultivation, there is both wasteful application of irrigation water and electricity in the cultivation of paddy crops, burning an unproductive hole in the exchequer’s pocket. There is limited access to both agricultural extension services and water-conserving technology, along with policy imbalance, keeping farmers in an intensive and unsustainable production system. Punjab agriculture is witnessing diminishing returns to factor, which under the business-as-usual scenario, will soon enter the phase of negative returns to factor.

Keywords: cropping pattern, electrification, subsidy, sustainability

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Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

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Authors: Manish Saha, Manish Kumar Niranjan, Saket Asthana

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The K₀.₅Na₀.₅NbO₃ (KNN) system has emerged as one of the most promising lead-free piezoelectric over the years. In this work, we perform a comprehensive investigation of electronic structure, lattice dynamics and dielectric/ferroelectric properties of the room temperature phase of KNN by combining ab-initio DFT-based theoretical analysis and experimental characterization. We assign the symmetry labels to KNN vibrational modes and obtain ab-initio polarized Raman spectra, Infrared (IR) reflectivity, Born-effective charge tensors, oscillator strengths etc. The computed Raman spectrum is found to agree well with the experimental spectrum. In particular, the results suggest that the mode in the range ~840-870 cm-¹ reported in the experimental studies is longitudinal optical (LO) with A_1 symmetry. The Raman mode intensities are calculated for different light polarization set-ups, which suggests the observation of different symmetry modes in different polarization set-ups. The electronic structure of KNN is investigated, and an optical absorption spectrum is obtained. Further, the performances of DFT semi-local, metal-GGA and hybrid exchange-correlations (XC) functionals, in the estimation of KNN band gaps are investigated. The KNN bandgap computed using GGA-1/2 and HSE06 hybrid functional schemes are found to be in excellant agreement with the experimental value. The COHP, electron localization function and Bader charge analysis is also performed to deduce the nature of chemical bonding in the KNN. The solid-state reaction and hydrothermal methods are used to prepare the KNN ceramics, and the effects of grain size on the physical characteristics these ceramics are examined. A comprehensive study on the impact of different synthesis techniques on the structural, electrical, and photocatalytic properties of ferroelectric ceramics KNN. The KNN-S prepared by solid-state method have significantly larger grain size as compared to that for KNN-H prepared by hydrothermal method. Furthermore, the KNN-S is found to exhibit higher dielectric, piezoelectric and ferroelectric properties as compared to KNN-H. On the other hand, the increased photocatalytic activity is observed in KNN-H as compared to KNN-S. As compared to the hydrothermal synthesis, the solid-state synthesis causes an increase in the relative dielectric permittivity (ε^') from 2394 to 3286, remnant polarization (P_r) from 15.38 to 20.41 μC/cm^², planer electromechanical coupling factor (k_p) from 0.19 to 0.28 and piezoelectric coefficient (d_33) from 88 to 125 pC/N. The KNN-S ceramics are also found to have a lower leakage current density, and higher grain resistance than KNN-H ceramic. The enhanced photocatalytic activity of KNN-H is attributed to relatively smaller particle sizes. The KNN-S and KNN-H samples are found to have degradation efficiencies of RhB solution of 20% and 65%, respectively. The experimental study highlights the importance of synthesis methods and how these can be exploited to tailor the dielectric, piezoelectric and photocatalytic properties of KNN. Overall, our study provides several bench-mark important results on KNN that have not been reported so far.

Keywords: lead-free piezoelectric, Raman intensity spectrum, electronic structure, first-principles calculations, solid state synthesis, photocatalysis, hydrothermal synthesis

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