Search results for: language function

Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta

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Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.

Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect

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Authors: Natasha Bhate

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Contraception is important in helping to reduce maternal and infant mortality rates by allowing women to control the number and spacing in-between their children. It also reduces the need for unsafe abortions. Women worldwide use contraception; however, the contraceptive prevalence rate is still relatively low in Central American countries like Guatemala. There is also an unmet need for contraception in Guatemala, which is more significant in rural, indigenous women due to barriers preventing contraceptive use. The study objective was to investigate and analyse the current barriers women face, in Guatemala, Panajachel and the surrounding areas, in using contraception, with a view of identifying ways to overcome these barriers. This included exploring the contraceptive barriers women believe exist and the influence of males in contraceptive decision making. The study took place at a charity in Panajachel, Guatemala, and had a cross-sectional, qualitative design to allow an in-depth understanding of information gathered. This particular study design was also chosen to help inform the charity with qualitative research analysis, in view of their intent to create a local reproductive health programme. A semi-structured interview design, including photo facilitation to improve cross-cultural communication, with interpreter assistance, was utilized. A pilot interview was initially conducted with small improvements required. Participants were recruited through purposive and convenience sampling. The study host at the charity acted as a gatekeeper; participants were identified through attendance of the charity’s women’s-initiative programme workshops. 20 participants were selected and agreed to study participation with two not attending; a total of 18 participants were interviewed in June 2017. Interviews were audio-recorded and data were stored on encrypted memory sticks. Framework analysis was used to analyse the data using NVivo11 software. The University of Leeds granted ethical approval for the research. Religion, language, the community, and fear of sickness were examples of existing contraceptive barrier themes recognized by many participants. The influence of men was also an important barrier identified, with themes of machismo and abuse preventing contraceptive use in some women. Women from more rural areas were believed to still face barriers which some participants did not encounter anymore, such as distance and affordability of contraceptives. Participants believed that informative workshops in various settings were an ideal method of overcoming existing contraceptive barriers and allowing women to be more empowered. The involvement of men in such workshops was also deemed important by participants to help reduce their negative influence in contraceptive usage. Overall, four recommendations following this study were made, including contraceptive educational courses, a gender equality campaign, couple-focused contraceptive workshops, and further qualitative research to gain a better insight into men’s opinions regarding women using contraception.

Keywords: barrier, contraception, machismo, religion

Procedia PDF Downloads 107

Authors: Naniek Widayati Priyomarsono

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Introduction: In beginning of Karaton formation, namely, era of Javanese kingdom town had the power region outside castle town (called as Mancanegara), settlement of karaton can function as “the space-between” and “space-defense”, besides it was one of components from governmental structure and karaton power at that time (internal servant/abdi dalem and sentana dalem). Upon the Independence of Indonesia in 1945 “Kingdom-City” converted its political status into part of democratic town managed by statutes based on the classification. The latter affects local culture hierarchy alteration due to the physical development and events. Dynamics of social economy activities in Kampung Karaton surrounded by buildings of Complex of Karaton Kasunanan ini, have impact on the urban system disturbed into the región. Also cultural region image fades away with the weak visual access from existant cultural artefacts. That development lacks of giving appreciation to the established region image providing identity of Karaton Kasunanan particularly and identity of Surakarta city in general. Method used is strategy of grounded theory research (research providing strong base of a theory). Research is focused on actors active and passive relevantly getting involved in change process of Karaton settlement. Data accumulated is “Investigation Focus” oriented on actors affecting that change either internal or external. Investigation results are coupled with field observation data, documentation, literature study, thus it takes accurate findings. Findings: Karaton village has potential products as attraction, possessing human resource support, strong motivation from society still living in that settlement, possessing facilities and means supports, tourism event-supporting facilities, cultural art institution, available fields or development area. Data analyzed: To get the expected result it takes restoration in social cultural development direction, and economy, with ways of: Doing social cultural development strategy, economy, and politics. To-do steps are program socialization of Karaton village as Tourism Village, economical development of local society, regeneration pattern, filtering, and selection of tourism development, integrated planning system development, development with persuasive approach, regulation, market mechanism, social cultural event sector development, political development for region activity sector. Summary: In case the restoration is done by getting society involved as subject of that settlement (active participation in the field), managed and packed interestingly and naturally with tourism-supporting facilities development, village of Karaton Kasunanan Surakarta is ready to receive visit of domestic and foreign tourists.

Keywords: karaton village, finding, restoration, economy, Indonesia

Procedia PDF Downloads 417

Authors: Amer Ait Sidhoum

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Interest in sustainability has gained ground among practitioners, academics and policy-makers due to growing stakeholders’ awareness of environmental and social concerns. This is particularly true for agriculture. However, relatively little research has been conducted on the quantification of social sustainability and the contribution of social issues to the agricultural production efficiency. This research's main objective is to propose a method for evaluating prices of social outputs, more precisely shadow prices, by allowing for the stochastic nature of agricultural production that is to say for production uncertainty. In this article, the assessment of social outputs’ shadow prices is conducted within the methodological framework of nonparametric Data Envelopment Analysis (DEA). An output-oriented directional distance function (DDF) is implemented to represent the technology of a sample of Catalan arable crop farms and derive the efficiency scores the overall production technology of our sample is assumed to be the intersection of two different sub-technologies. The first sub-technology models the production of random desirable agricultural outputs, while the second sub-technology reflects the social outcomes from agricultural activities. Once a nonparametric production technology has been represented, the DDF primal approach can be used for efficiency measurement, while shadow prices are drawn from the dual representation of the DDF. Computing shadow prices is a method to assign an economic value to non-marketed social outcomes. Our research uses cross sectional, farm-level data collected in 2015 from a sample of 180 Catalan arable crop farms specialized in the production of cereals, oilseeds and protein (COP) crops. Our results suggest that our sample farms show high performance scores, from 85% for the bad state of nature to 88% for the normal and ideal crop growing conditions. This suggests that farm performance is increasing with an improvement in crop growth conditions. Results also show that average shadow prices of desirable state-contingent output and social outcomes for efficient and inefficient farms are positive, suggesting that the production of desirable marketable outputs and of non-marketable outputs makes a positive contribution to the farm production efficiency. Results also indicate that social outputs’ shadow prices are contingent upon the growing conditions. The shadow prices follow an upward trend as crop-growing conditions improve. This finding suggests that these efficient farms prefer to allocate more resources in the production of desirable outputs than of social outcomes. To our knowledge, this study represents the first attempt to compute shadow prices of social outcomes while accounting for the stochastic nature of the production technology. Our findings suggest that the decision-making process of the efficient farms in dealing with social issues are stochastic and strongly dependent on the growth conditions. This implies that policy-makers should adjust their instruments according to the stochastic environmental conditions. An optimal redistribution of rural development support, by increasing the public payment with the improvement in crop growth conditions, would likely enhance the effectiveness of public policies.

Keywords: data envelopment analysis, shadow prices, social sustainability, sustainable farming

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Authors: M. Ciminello, I. Dimino, S. Ameduri, A. Concilio

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Improving aircraft's efficiency is one of the key elements of Aeronautics. Modern aircraft possess many advanced functions, such as good transportation capability, high Mach number, high flight altitude, and increasing rate of climb. However, no aircraft has a possibility to reach all of this optimized performance in a single airframe configuration. The aircraft aerodynamic efficiency varies considerably depending on the specific mission and on environmental conditions within which the aircraft must operate. Structures that morph their shape in response to their surroundings may at first seem like the stuff of science fiction, but take a look at nature and lots of examples of plants and animals that adapt to their environment would arise. In order to ensure both the controllable and the static robustness of such complex structural systems, a monitoring network is aimed at verifying the effectiveness of the given control commands together with the elastic response. In order to achieve this kind of information, the use of FBG sensors network is, in this project, proposed. The sensor network is able to measure morphing structures shape which may show large, global displacements due to non-standard architectures and materials adopted. Chord -wise variations may allow setting and chasing the best layout as a function of the particular and transforming reference state, always targeting best aerodynamic performance. The reason why an optical sensor solution has been selected is that while keeping a few of the contraindication of the classical systems (like cabling, continuous deployment, and so on), fibre optic sensors may lead to a dramatic reduction of the wires mass and weight thanks to an extreme multiplexing capability. Furthermore, the use of the ‘light’ as ‘information carrier’, permits dealing with nimbler, non-shielded wires, and avoids any kind of interference with the on-board instrumentation. The FBG-based transducers, herein presented, aim at monitoring the actual shape of adaptive trailing edge. Compared to conventional systems, these transducers allow more fail-safe measurements, by taking advantage of a supporting structure, hosting FBG, whose properties may be tailored depending on the architectural requirements and structural constraints, acting as strain modulator. The direct strain may, in fact, be difficult because of the large deformations occurring in morphing elements. A modulation transducer is then necessary to keep the measured strain inside the allowed range. In this application, chord-wise transducer device is a cantilevered beam sliding trough the spars and copying the camber line of the ATE ribs. FBG sensors array position are dimensioned and integrated along the path. A theoretical model describing the system behavior is implemented. To validate the design, experiments are then carried out with the purpose of estimating the functions between rib rotation and measured strain.

Keywords: fiber optic sensor, morphing structures, strain sensor, shape reconstruction

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Authors: Mohammad Javaherian, Siamak Bashardoust Tajali, Monavvar Hadizadeh

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Objective: This systematic review study was conducted to evaluate the effects of Pulsed Electromagnetic (PEMF) and Static Magnetic Fields (SMG) on pain relief and functional improvement in patients with musculoskeletal Low Back Pain (LBP). Methods: Seven electronic databases were searched by two researchers independently to identify the published Randomized Controlled Trials (RCTs) on the efficacy of pulsed electromagnetic, static magnetic, and therapeutic nuclear magnetic fields. The identified databases for systematic search were Ovid Medline®, Ovid Cochrane RCTs and Reviews, PubMed, Web of Science, Cochrane Library, CINAHL, and EMBASE from 1968 to February 2016. The relevant keywords were selected by Mesh. After initial search and finding relevant manuscripts, all references in selected studies were searched to identify second hand possible manuscripts. The published RCTs in English would be included to the study if they reported changes on pain and/or functional disability following application of magnetic fields on chronic musculoskeletal low back pain. All studies with surgical patients, patients with pelvic pain, and combination of other treatment techniques such as acupuncture or diathermy were excluded. The identified studies were critically appraised and the data were extracted independently by two raters (M.J and S.B.T). Probable disagreements were resolved through discussion between raters. Results: In total, 1505 abstracts were found following the initial electronic search. The abstracts were reviewed to identify potentially relevant manuscripts. Seventeen possibly appropriate studies were retrieved in full-text of which 48 were excluded after reviewing their full-texts. Ten selected articles were categorized into three subgroups: PEMF (6 articles), SMF (3 articles), and therapeutic nuclear magnetic fields (tNMF) (1 article). Since one study evaluated tNMF, we had to exclude it. In the PEMF group, one study of acute LBP did not show significant positive results and the majority of the other five studies on Chronic Low Back Pain (CLBP) indicated its efficacy on pain relief and functional improvement, but one study with the lowest sessions (6 sessions during 2 weeks) did not report a significant difference between treatment and control groups. In the SMF subgroup, two articles reported near significant pain reduction without any functional improvement although more studies are needed. Conclusion: The PEMFs with a strength of 5 to 150 G or 0.1 to 0.3 G and a frequency of 5 to 64 Hz or sweep 7 to 7KHz can be considered as an effective modality in pain relief and functional improvement in patients with chronic low back pain, but there is not enough evidence to confirm their effectiveness in acute low back pain. To achieve the appropriate effectiveness, it is suggested to perform this treatment modality 20 minutes per day for at least 9 sessions. SMFs have not been reported to be substantially effective in decreasing pain or improving the function in chronic low back pain. More studies are necessary to achieve more reliable results.

Keywords: pulsed electromagnetic field, static magnetic field, magnetotherapy, low back pain

Procedia PDF Downloads 185

Authors: Margarita Ivanova, Julia Dao, Andrew Friedman, Neil Kasaci, Rekha Gopal, Ozlem Goker-Alpan

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In Fabry disease (FD), α-galactosidase A (α-Gal A) deficiency leads to the accumulation of globotriaosylceramide (Lyso-Gb3 and Gb3), triggering a pathologic cascade that causes the severity of organs damage. The heart is one of the several organs with high sensitivity to the α-Gal A deficiency. A subgroup of patients with significant residual of α-Gal A activity with primary cardiac involvement is occasionally referred to as “cardiac variant.” The cardiovascular complications are most frequently encountered, contributing substantially to morbidity, and are the leading cause of premature death in male and female patients with FD. The deposition of Lyso-Gb-3 and Gb-3 within the myocardium affects cardiac function with resultant progressive cardiovascular pathology. Gb-3 and Lyso-Gb-3 accumulation at the cellular level trigger a cascade of events leading to end-stage fibrosis. In the cardiac tissue, Lyso-Gb-3 deposition is associated with the increased release of inflammatory factors and transforming growth factors. Infiltration of lymphocytes and macrophages into endomyocardial tissue indicates that inflammation plays a significant role in cardiac damage. Moreover, accumulated data suggest that chronic inflammation leads to multisystemic FD pathology even under enzyme replacement therapy (ERT). NF-κB activation plays a subsequent role in the inflammatory response to cardiac dysfunction and advanced heart failure in the general population. TNFalpha/NF-κB signaling protects the myocardial evoking by ischemic preconditioning; however, this protective effect depends on the concentration of TNF-α. Thus, we hypothesize that TNF-α is a critical factor in determining the grade of cardio-pathology. Cardiac hypertrophy corresponds to the expansion of the coronary vasculature to maintain a sufficient supply of nutrients and oxygen. Coronary activation of angiogenesis and fibrosis plays a vital role in cardiac vascularization, hypertrophy, and tissue remodeling. We suggest that the interaction between the inflammatory pathways and cardiac vascularization is a bi-directional process controlled by secreted cytokines and growth factors. The co-coordination of these two processes has never been explored in FD. In a cohort of 40 patients with FD, biomarkers associated with inflammation and cardio hypertrophic remodeling were studied. FD patients were categorized into three groups based on LVmass/DSA, LVEF, and ECG abnormalities: FD with no cardio complication, FD with moderate cardio complication, and severe cardio complication. Serum levels of NF-kB, TNFalpha, Il-6, Il-2, MCP1, ING-gamma, VEGF, IGF-1, TGFβ, and FGF2 were quantified by enzyme-linked immunosorbent assays (ELISA). Among the biomarkers, MCP-1, INF-gamma, VEGF, TNF-alpha, and TGF-beta were elevated in FD patients. Some of these biomarkers also have the potential to correlate with cardio pathology in FD. Conclusion: The study provides information about the role of inflammatory pathways and biomarkers of cardio hypertrophic remodeling in FD patients. This study will also reveal the mechanisms that link intracellular accumulation of Lyso-GB-3 and Gb3 to the development of cardiomyopathy with myocardial thickening and resultant fibrosis.

Keywords: biomarkers, Fabry disease, inflammation, growth factors

Procedia PDF Downloads 62

Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

Procedia PDF Downloads 358

Authors: Mari Jaakkola, Jasmiina Haverinen, Tiina Tolonen, Vesa Virtanen

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These process monitoring of biogas plant gives valuable information of the function of the process and help to maintain a stable process. The costs of basic monitoring are often much lower than the costs associated with re-establishing a biologically destabilised plant. Reactor acidification through reactor overload is one of the most common reasons for process deterioration in anaerobic digesters. This occurs because of a build-up of volatile fatty acids (VFAs) produced by acidogenic and acetogenic bacteria. VFAs cause pH values to decrease, and result in toxic conditions in the reactor. Ammonia ensures an adequate supply of nitrogen as a nutrient substance for anaerobic biomass and increases system's buffer capacity, counteracting acidification lead by VFA production. However, elevated ammonia concentration is detrimental to the process due to its toxic effect. VFAs are considered the most reliable analytes for process monitoring. To obtain accurate results, sample storage and transportation need to be carefully controlled. This may be a challenge for off-line laboratory analyses especially when the plant is located far away from the laboratory. The aim of this study was to investigate the correlation between fatty acids, ammonium, and bacteria in the anaerobic digestion samples obtained from an industrial biogas factory. The stability of the analytes was studied comparing the results of the on-site analyses performed in the factory site to the results of the samples stored at room temperature and -18°C (up to 30 days) after sampling. Samples were collected in the biogas plant consisting of three separate mesofilic AD reactors (4000 m³ each) where the main feedstock was swine slurry together with a complex mixture of agricultural plant and animal wastes. Individual VFAs, ammonium, and nutrients (K, Ca, Mg) were studied by capillary electrophoresis (CE). Longer chain fatty acids (oleic, hexadecanoic, and stearic acids) and bacterial profiles were studied by GC-MSD (Gas Chromatography-Mass Selective Detector) and 16S rDNA, respectively. On-site monitoring of the analytes was performed by CE. The main VFA in all samples was acetic acid. However, in one reactor sample elevated levels of several individual VFAs and long chain fatty acids were detected. Also bacterial profile of this sample differed from the profiles of other samples. Acetic acid decomposed fast when the sample was stored in a room temperature. All analytes were stable when stored in a freezer. Ammonium was stable even at a room temperature for the whole testing period. One reactor sample had higher concentration of VFAs and long chain fatty acids than other samples. CE was utilized successfully in the on-site analysis of separate VFAs and NH₄ in the biogas production site. Samples should be analysed in the sampling day if stored in RT or freezed for longer storage time. Fermentation reject can be stored (and transported) at ambient temperature at least for one month without loss of NH₄. This gives flexibility to the logistic solutions when reject is used as a fertilizer.

Keywords: anaerobic digestion, capillary electrophoresis, ammonium, bacteria

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Authors: Kaleeswari R. K., Seevagan L .

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Soil quality in an agroecosystem is influenced by the cropping system, water and soil fertility management. A valid soil quality index would help to assess the soil and crop management practices for desired productivity and soil health. The soil quality indices also provide an early indication of soil degradation and needy remedial and rehabilitation measures. Imbalanced fertilization and inadequate organic carbon dynamics deteriorate soil quality in an intensive cropping system. The rice soil ecosystem is different from other arable systems since rice is grown under submergence, which requires a different set of key soil attributes for enhancing soil quality and productivity. Assessment of the soil quality index involves indicator selection, indicator scoring and comprehensive score into one index. The most appropriate indicator to evaluate soil quality can be selected by establishing the minimum data set, which can be screened by linear and multiple regression factor analysis and score function. This investigation was carried out in intensive rice cultivating regions (having >1.0 lakh hectares) of Tamil Nadu viz., Thanjavur, Thiruvarur, Nagapattinam, Villupuram, Thiruvannamalai, Cuddalore and Ramanathapuram districts. In each district, intensive rice growing block was identified. In each block, two sampling grids (10 x 10 sq.km) were used with a sampling depth of 10 – 15 cm. Using GIS coordinates, and soil sampling was carried out at various locations in the study area. The number of soil sampling points were 41, 28, 28, 32, 37, 29 and 29 in Thanjavur, Thiruvarur, Nagapattinam, Cuddalore, Villupuram, Thiruvannamalai and Ramanathapuram districts, respectively. Principal Component Analysis is a data reduction tool to select some of the potential indicators. Principal Component is a linear combination of different variables that represents the maximum variance of the dataset. Principal Component that has eigenvalues equal or higher than 1.0 was taken as the minimum data set. Principal Component Analysis was used to select the representative soil quality indicators in rice soils based on factor loading values and contribution percent values. Variables having significant differences within the production system were used for the preparation of the minimum data set. Each Principal Component explained a certain amount of variation (%) in the total dataset. This percentage provided the weight for variables. The final Principal Component Analysis based soil quality equation is SQI = ∑ i=1 (W ᵢ x S ᵢ); where S- score for the subscripted variable; W-weighing factor derived from PCA. Higher index scores meant better soil quality. Soil respiration, Soil available Nitrogen and Potentially Mineralizable Nitrogen were assessed as soil quality indicators in rice soil of the Cauvery Delta zone covering Thanjavur, Thiruvavur and Nagapattinam districts. Soil available phosphorus could be used as a soil quality indicator of rice soils in the Cuddalore district. In rain-fed rice ecosystems of coastal sandy soil, DTPA – Zn could be used as an effective soil quality indicator. Among the soil parameters selected from Principal Component Analysis, Microbial Biomass Nitrogen could be used quality indicator for rice soils of the Villupuram district. Cauvery Delta zone has better SQI as compared with other intensive rice growing zone of Tamil Nadu.

Keywords: soil quality index, soil attributes, soil mapping, and rice soil

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Authors: Szerena Vajkovszki

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Among the relatively large volume of literature, the role and perception of women in Buddhism have been examined from various perspectives such as theology, history, anthropology, and feminism. When Buddhism spread to the West, women had a major role in its adaption and development. The meeting of different cultures and social structures had the fruit of a necessity to change. As Buddhism gained attention in the West, it produced a Buddhist feminist identity across national and ethnic boundaries. So globalization produced a contemporary cross-cultural Buddhist Women. The aim of the research is to find out the new role of such a Buddhist woman in aging societies. More precisely to understand what effect this contemporary Buddhist religion may have, direct or indirect, on fertility. Our worldwide aging society, especially in developed countries, including members of EU, raise sophisticated sociological and economic issues and challenges to be met. As declining fertility has outstanding influence underlying this trend, numerous studies have attempted to identify, describe, measure and interpret contributing factors of the fertility rate, out of which relatively few revealed the impact of religion. Among many religious guidelines, we can separate two major categories: direct and indirect. The aim of this research was to understand what are the most crucial identified (family values, gender related behaviors, religious sentiments) and not yet identified most influential contributing contemporary Buddhist religious factors. Above identifying these direct or indirect factors, it is also important to understand to what extent and how do they influence fertility, which requires a wider (inter-discipline) perspective. As proved by previous studies religion has also an influential role in health, mental state, well-being, working activity and many other components that are also related to fertility rates. All these components are inter-related, hence direct and indirect religious effects can only be well understood, if we figure out all necessary fields and their interaction. With the help of semi-structured opened interviews taking place in different countries, it was showed that indeed Buddhism has significant direct and indirect effect on fertility, hence the initial hypothesis was proved. However, the interviews showed an overall positive effect, the results could only serve for a general understanding about how Buddhism affects fertility. Evolution of Buddhism’s direct and indirect influence may vary in different nations and circumstances according to their specific environmental attributes. According to the local patterns, with special regard to women’s position and role in the society, outstandingly indirect influences could show diversifications. So it is advisory to investigate more for a deeper and clearer understanding of how Buddhism function in different socioeconomic circumstances. For example, in Hungary after the period of secularization more and more people tended to be attracted toward some transcendent values which could be an explanation for the rising number of Buddhists in the country. The present research could serve as a general starting point or a common basis for further specific national investigations how contemporary Buddhism affects fertility.

Keywords: contemporary Buddhism, cross-cultural woman, fertility, gender roles, religion

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Authors: Tomola Obamuyi

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The banking system in Nigeria adopted innovative banking, with the aim of enhancing financial inclusion, and making financial services readily and cheaply available to majority of the people, and to contribute to the efficiency of the financial system. Some of the innovative services include: Automatic Teller Machines (ATMs), National Electronic Fund Transfer (NEFT), Point of Sale (PoS), internet (Web) banking, Mobile Money payment (MMO), Real-Time Gross Settlement (RTGS), agent banking, among others. The introduction of these payment systems is expected to increase bank efficiency and customers' satisfaction, culminating in better performance for the commercial banks. However, opinions differ on the possible effects of the various innovative payment systems on the performance of commercial banks in the country. Thus, this study empirically determines how commercial banks use innovation to gain competitive advantage in the specific context of Nigeria's finance and business. The study also analyses the effects of financial innovation on the performance of commercial banks, when different periods of analysis are considered. The study employed secondary data from 2009 to 2018, the period that witnessed aggressive innovation in the financial sector of the country. The Vector Autoregression (VAR) estimation technique forecasts the relative variance of each random innovation to the variables in the VAR, examine the effect of standard deviation shock to one of the innovations on current and future values of the impulse response and determine the causal relationship between the variables (VAR granger causality test). The study also employed the Multi-Criteria Decision Making (MCDM) to rank the innovations and the performance criteria of Return on Assets (ROA) and Return on Equity (ROE). The entropy method of MCDM was used to determine which of the performance criteria better reflect the contributions of the various innovations in the banking sector. On the other hand, the Range of Values (ROV) method was used to rank the contributions of the seven innovations to performance. The analysis was done based on medium term (five years) and long run (ten years) of innovations in the sector. The impulse response function derived from the VAR system indicated that the response of ROA to the values of cheques transaction, values of NEFT transactions, values of POS transactions was positive and significant in the periods of analysis. The paper also confirmed with entropy and range of value that, in the long run, both the CHEQUE and MMO performed best while NEFT was next in performance. The paper concluded that commercial banks would enhance their performance by continuously improving on the services provided through Cheques, National Electronic Fund Transfer and Point of Sale since these instruments have long run effects on their performance. This will increase the confidence of the populace and encourage more usage/patronage of these services. The banking sector will in turn experience better performance which will improve the economy of the country. Keywords: Bank performance, financial innovation, multi-criteria decision making, vector autoregression,

Keywords: Bank performance, financial innovation, multi-criteria decision making, vector autoregression

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Authors: Adriana Anselmo Oliveira

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

Keywords: Vieira da Silva, tiles, conservation, restoration

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Authors: Sonia P. Marrero Duran, Lilian Noya Dominguez, Lisandra Quintana Alvarez, Evert Martinez Perez, Ana Julia Acevedo Urquiaga

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Cuban business and economic policy are in the constant update as well as facing a client ever more knowledgeable and demanding. For that reason become fundamental for companies competitiveness through the optimization of its processes and services. One of the Cuban’s pillars, which has been sustained since the triumph of the Cuban Revolution back in 1959, is the free health service to all those who need it. This service is offered without any charge under the concept of preserving human life, but it implied costly management processes and logistics services to be able to supply the necessary medicines to all the units who provide health services. One of the key actors on the medicine supply chain is the Havana Distribution Center (HDC), which is responsible for the delivery of medicines in the province; as well as the acquisition of medicines from national and international producers and its subsequent transport to health care units and pharmacies in time, and with the required quality. This HDC also carries for all distribution centers in the country. Given the eminent need to create an actor in the supply chain that specializes in the medicines supply, the possibility of centralizing this operation in a logistics service provider is analyzed. Based on this decision, pharmacies operate as clients of the logistic service center whose main function is to centralize all logistics operations associated with the medicine supply chain. The HDC is precisely the logistic service provider in Havana and it is the center of this research. In 2017 the pharmacies had affectations in the availability of medicine due to deficiencies in the distribution routes. This is caused by the fact that they are not based on routing studies, besides the long distribution cycle. The distribution routs are fixed, attend only one type of customer and there respond to a territorial location by the municipality. Taking into consideration the above-mentioned problem, the objective of this research is to optimize the routes system in the Havana Distribution Center. To accomplish this objective, the techniques applied were document analysis, random sampling, statistical inference and tools such as Ishikawa diagram and the computerized software’s: ArcGis, Osmand y MapIfnfo. As a result, were analyzed four distribution alternatives; the actual rout, by customer type, by the municipality and the combination of the two last. It was demonstrated that the territorial location alternative does not take full advantage of the transportation capacities or the distance of the trips, which leads to elevated costs breaking whit the current ways of distribution and the currents characteristics of the clients. The principal finding of the investigation was the optimum option distribution rout is the 4th one that is formed by hospitals and the join of pharmacies, stomatology clinics, polyclinics and maternal and elderly homes. This solution breaks the territorial location by the municipality and permits different distribution cycles in dependence of medicine consumption and transport availability.

Keywords: computerized geographic software, distribution, distribution routs, vehicle problem routing (VPR)

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Authors: George Zhou, Yunchan Chen, Candace Chien

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Kidney replacement therapy is the current standard of care for end-stage renal diseases. In-center or home hemodialysis remains an integral component of the therapeutic regimen. Arteriovenous fistulas (AVF) make up the vascular circuit through which blood is filtered and returned. Naturally, AVF patency determines whether adequate clearance and filtration can be achieved and directly influences clinical outcomes. Our aim was to build a deep learning model for automated AVF stenosis screening based on the sound of blood flow through the AVF. A total of 311 patients with AVF were enrolled in this study. Blood flow sounds were collected using a digital stethoscope. For each patient, blood flow sounds were collected at 6 different locations along the patient’s AVF. The 6 locations are artery, anastomosis, distal vein, middle vein, proximal vein, and venous arch. A total of 1866 sounds were collected. The blood flow sounds are labeled as “patent” (normal) or “stenotic” (abnormal). The labels are validated from concurrent ultrasound. Our dataset included 1527 “patent” and 339 “stenotic” sounds. We show that blood flow sounds vary significantly along the AVF. For example, the blood flow sound is loudest at the anastomosis site and softest at the cephalic arch. Contextualizing the sound with location metadata significantly improves classification performance. How to encode and incorporate categorical metadata is an active area of research1. Herein, we study ordinal (i.e., integer) encoding schemes. The numerical representation is concatenated to the flattened feature vector. We train a vision transformer (ViT) on spectrogram image representations of the sound and demonstrate that using scalar multiples of our integer encodings improves classification performance. Models are evaluated using a 10-fold cross-validation procedure. The baseline performance of our ViT without any location metadata achieves an AuROC and AuPRC of 0.68 ± 0.05 and 0.28 ± 0.09, respectively. Using the following encodings of Artery:0; Arch: 1; Proximal: 2; Middle: 3; Distal 4: Anastomosis: 5, the ViT achieves an AuROC and AuPRC of 0.69 ± 0.06 and 0.30 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 10; Proximal: 20; Middle: 30; Distal 40: Anastomosis: 50, the ViT achieves an AuROC and AuPRC of 0.74 ± 0.06 and 0.38 ± 0.10, respectively. Using the following encodings of Artery:0; Arch: 100; Proximal: 200; Middle: 300; Distal 400: Anastomosis: 500, the ViT achieves an AuROC and AuPRC of 0.78 ± 0.06 and 0.43 ± 0.11. respectively. Interestingly, we see that using increasing scalar multiples of our integer encoding scheme (i.e., encoding “venous arch” as 1,10,100) results in progressively improved performance. In theory, the integer values do not matter since we are optimizing the same loss function; the model can learn to increase or decrease the weights associated with location encodings and converge on the same solution. However, in the setting of limited data and computation resources, increasing the importance at initialization either leads to faster convergence or helps the model escape a local minimum.

Keywords: arteriovenous fistula, blood flow sounds, metadata encoding, deep learning

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Authors: Susmita Ghosh

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Catchment area of Damodar River, India experiences seasonal rains due to the south-west monsoon every year and depending upon the intensity of the storms, floods occur. During the monsoon season, the rainfall in the area is mainly due to active monsoon conditions. The upstream reach of Damodar river system has five dams store the water for utilization for various purposes viz, irrigation, hydro-power generation, municipal supplies and last but not the least flood moderation. But, in the downstream reach of Damodar River, known as Lower Damodar region, is severely and frequently suffering from flood due to heavy monsoon rainfall and also release from upstream reservoirs. Therefore, an effective flood management study is required to know in depth the nature and extent of flood, water logging, and erosion related problems, affected area, and damages in the Lower Damodar region, by conducting mathematical model study. The design flood or discharge is needed to decide to assign the respective model for getting several scenarios from the simulation runs. The ultimate aim is to achieve a sustainable flood management scheme from the several alternatives. there are various methods for estimating flood discharges to be carried through the rivers and their tributaries for quick drainage from inundated areas due to drainage congestion and excess rainfall. In the present study, the flood frequency analysis is performed to decide the design flood discharge of the study area. This, on the other hand, has limitations in respect of availability of long peak flood data record for determining long type of probability density function correctly. If sufficient past records are available, the maximum flood on a river with a given frequency can safely be determined. The floods of different frequency for the Damodar has been calculated by five candidate distributions i.e., generalized extreme value, extreme value-I, Pearson type III, Log Pearson and normal. Annual peak discharge series are available at Durgapur barrage for the period of 1979 to 2013 (35 years). The available series are subjected to frequency analysis. The primary objective of the flood frequency analysis is to relate the magnitude of extreme events to their frequencies of occurrence through the use of probability distributions. The design flood for return periods of 10, 15 and 25 years return period at Durgapur barrage are estimated by flood frequency method. It is necessary to develop flood hydrographs for the above floods to facilitate the mathematical model studies to find the depth and extent of inundation etc. Null hypothesis that the distributions fit the data at 95% confidence is checked with goodness of fit test, i.e., Chi Square Test. It is revealed from the goodness of fit test that the all five distributions do show a good fit on the sample population and is therefore accepted. However, it is seen that there is considerable variation in the estimation of frequency flood. It is therefore considered prudent to average out the results of these five distributions for required frequencies. The inundated area from past data is well matched using this flood.

Keywords: design discharge, flood frequency, goodness of fit, sustainable flood management

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Authors: Ifeyinwa Victor-Uadiale, Georgina Pearson, Sophie Witter, D. Reidpath

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Introduction: Smoking, alcohol misuse, unhealthy diet, and physical inactivity are the primary drivers of noncommunicable diseases (NCD), including cardiovascular diseases, cancers, respiratory diseases, and diabetes, worldwide. Collectively, these diseases are the leading cause of all global deaths, most of which are premature, affecting people between 30 and 70 years. Empirical evidence suggests that these risk behaviors can be modified by community-based interventions (CBI). However, there is little insight into the mechanisms and contextual factors of successful community interventions that impact risk behaviours for chronic diseases. This study examined “Under what circumstances, for whom, and how, do community-based interventions modify smoking, alcohol use, unhealthy diet, and physical inactivity among adults”. Adopting the Capability (C), Opportunity (O), Motivation (M), Behavior (B) (COM-B) framework for behaviour change, it sought to: (1) identify the mechanisms through which CBIs could reduce tobacco use and alcohol consumption and increase physical activity and the consumption of healthy diets and (2) examine the contextual factors that trigger the impact of these mechanisms on these risk behaviours among adults. Methods: Pawson’s realist review method was used to examine the literature. Empirical evidence and theoretical understanding were combined to develop a realist program theory that explains how CBIs influence NCD risk behaviours. Documents published between 2002 and 2020 were systematically searched in five electronic databases (CINAHL, Cochrane Library, Medline, ProQuest Central, and PsycINFO). They were included if they reported on community-based interventions aimed at cardiovascular diseases, cancers, respiratory diseases, and diabetes in a global context; and had an outcome targeted at smoking, alcohol, physical activity, and diet. Findings: Twenty-nine scientific documents were retrieved and included in the review. Over half of them (n = 18; 62%) focused on three of the four risk behaviours investigated in this review. The review identified four mechanisms: capability, opportunity, motivation, and social support that are likely to change the dietary and physical activity behaviours in adults given certain contexts. There were weak explanations of how the identified mechanisms could likely change smoking and alcohol consumption habits. In addition, eight contextual factors that may affect how these mechanisms impact physical activity and dietary behaviours were identified: suitability to work and family obligations, risk status awareness, socioeconomic status, literacy level, perceived need, availability and access to resources, culture, and group format. Conclusion: The findings suggest that CBIs are likely to improve the physical activity and dietary habits of adults if the intervention function seeks to educate, incentivize, change the environment, and model the right behaviours. The review applies and advances theory, realist research, and the design and implementation of community-based interventions for NCD prevention.

Keywords: community-based interventions, noncommunicable disease, realist program theory, risk behaviors

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Authors: Liu Jia’nan

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The default accounts hold the view that there exists a kind of scalar implicature which can be processed without context and own a psychological privilege over other scalar implicatures which depend on context. In contrast, the Relevance Theorist regards context as a must because all the scalar implicatures have to meet the need of relevance in discourse. However, in Katsos, the experimental results showed: Although quantitatively the adults rejected under-informative utterance with lexical scales (context-independent) and the ad hoc scales (context-dependent) at almost the same rate, adults still regarded the violation of utterance with lexical scales much more severe than with ad hoc scales. Neither default account nor Relevance Theory can fully explain this result. Thus, there are two questionable points to this result: (1) Is it possible that the strange discrepancy is due to other factors instead of the generation of scalar implicature? (2) Are the ad hoc scales truly formed under the possible influence from mental context? Do the participants generate scalar implicatures with ad hoc scales instead of just comparing semantic difference among target objects in the under- informative utterance? In my Experiment 1, the question (1) will be answered by repetition of Experiment 1 by Katsos. Test materials will be showed by PowerPoint in the form of pictures, and each procedure will be done under the guidance of a tester in a quiet room. Our Experiment 2 is intended to answer question (2). The test material of picture will be transformed into the literal words in DMDX and the target sentence will be showed word-by-word to participants in the soundproof room in our lab. Reading time of target parts, i.e. words containing scalar implicatures, will be recorded. We presume that in the group with lexical scale, standardized pragmatically mental context would help generate scalar implicature once the scalar word occurs, which will make the participants hope the upcoming words to be informative. Thus if the new input after scalar word is under-informative, more time will be cost for the extra semantic processing. However, in the group with ad hoc scale, scalar implicature may hardly be generated without the support from fixed mental context of scale. Thus, whether the new input is informative or not does not matter at all, and the reading time of target parts will be the same in informative and under-informative utterances. People’s mind may be a dynamic system, in which lots of factors would co-occur. If Katsos’ experimental result is reliable, will it shed light on the interplay of default accounts and context factors in scalar implicature processing? We might be able to assume, based on our experiments, that one single dominant processing paradigm may not be plausible. Furthermore, in the processing of scalar implicature, the semantic interpretation and the pragmatic interpretation may be made in a dynamic interplay in the mind. As to the lexical scale, the pragmatic reading may prevail over the semantic reading because of its greater exposure in daily language use, which may also lead the possible default or standardized paradigm override the role of context. However, those objects in ad hoc scale are not usually treated as scalar membership in mental context, and thus lexical-semantic association of the objects may prevent their pragmatic reading from generating scalar implicature. Only when the sufficient contextual factors are highlighted, can the pragmatic reading get privilege and generate scalar implicature.

Keywords: scalar implicature, ad hoc scale, dynamic interplay, default account, Mandarin Chinese processing

Procedia PDF Downloads 294

Authors: Cristina Opris, Bogdan Cojocaru, Madalina Tudorache, Simona M. Coman, Vasile I. Parvulescu, Camelia Bala, Bahir Duraki, Jeroen A. Van Bokhoven

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The tremendous achievements in the development of the society concretized by more sophisticated materials and systems are merely based on non-renewable resources. Consequently, after more than two centuries of intensive development, among others, we are faced with the decrease of the fossil fuel reserves, an increased impact of the greenhouse gases on the environment, and economic effects caused by the fluctuations in oil and mineral resource prices. The use of biomass may solve part of these problems, and recent analyses demonstrated that from the perspective of the reduction of the emissions of carbon dioxide, its valorization may bring important advantages conditioned by the usage of genetic modified fast growing trees or wastes, as primary sources. In this context, the abundance and complex structure of lignin may offer various possibilities of exploitation. However, its transformation in fuels or chemicals supposes a complex chemistry involving the cleavage of C-O and C-C bonds and altering of the functional groups. Chemistry offered various solutions in this sense. However, despite the intense work, there are still many drawbacks limiting the industrial application. Thus, the proposed technologies considered mainly homogeneous catalysts meaning expensive noble metals based systems that are hard to be recovered at the end of the reaction. Also, the reactions were carried out in organic solvents that are not acceptable today from the environmental point of view. To avoid these problems, the concept of this work was to investigate the synthesis of superparamagnetic core shell catalysts for the fragmentation of lignin directly in the aqueous phase. The magnetic nanoparticles were covered with a nanoshell of an oxide (niobia) with a double role: to protect the magnetic nanoparticles and to generate a proper (acidic) catalytic function and, on this composite, cobalt nanoparticles were deposed in order to catalyze the C-C bond splitting. With this purpose, we developed a protocol to prepare multifunctional and magnetic separable nano-composite Co@Nb2O5@Fe3O4 catalysts. We have also established an analytic protocol for the identification and quantification of the fragments resulted from lignin depolymerization in both liquid and solid phase. The fragmentation of various lignins occurred on the prepared materials in high yields and with very good selectivity in the desired fragments. The optimization of the catalyst composition indicated a cobalt loading of 4wt% as optimal. Working at 180 oC and 10 atm H2 this catalyst allowed a conversion of lignin up to 60% leading to a mixture containing over 96% in C20-C28 and C29-C37 fragments that were then completely fragmented to C12-C16 in a second stage. The investigated catalysts were completely recyclable, and no leaching of the elements included in the composition was determined by inductively coupled plasma optical emission spectrometry (ICP-OES).

Keywords: superparamagnetic core-shell catalysts, environmental production of fuels, renewable lignin, recyclable catalysts

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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

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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

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Authors: Alexander Huang

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Online learning sessions have become an indispensable complement to in-classroom-learning sessions in the past two years due to the emergence of Covid-19. Due to social distance requirements, many courses and interaction-intensive sessions, ranging from music classes to debate camps, are online. However, online learning imposes a significant challenge for engaging students effectively during the learning sessions. To resolve this problem, Project PWR, a non-profit organization formed by high school students, developed an online kid-teach-kid learning environment to boost students' learning interests and further improve students’ engagement during online learning. Fundamentally, the kid-teach-kid learning model creates an affinity space to form learning groups, where like-minded peers can learn and teach their interests. The role of the teacher can also help a kid identify the instructional task and set the rules and procedures for the activities. The approach also structures initial discussions to reveal a range of ideas, similar experiences, thinking processes, language use, and lower student-to-teacher ratio, which become enriched online learning experiences for upcoming lessons. In such a manner, a kid can practice both the teacher role and the student role to accumulate experiences on how to convey ideas and questions over the online session more efficiently and effectively. In this research work, we conducted two case studies involving a 3D-Design course and a Speech and Debate course taught by high-school kids. Through Project PWR, a kid first needs to design the course syllabus based on a provided template to become a student-teacher. Then, the Project PWR academic committee evaluates the syllabus and offers comments and suggestions for changes. Upon the approval of a syllabus, an experienced and voluntarily adult mentor is assigned to interview the student-teacher and monitor the lectures' progress. Student-teachers construct a comprehensive final evaluation for their students, which they grade at the end of the course. Moreover, each course requires conducting midterm and final evaluations through a set of surveyed replies provided by students to assess the student-teacher’s performance. The uniqueness of Project PWR lies in its established kid-teach-kids affinity space. Our research results showed that Project PWR could create a closed-loop system where a student can help a teacher improve and vice versa, thus improving the overall students’ engagement. As a result, Project PWR’s approach can train teachers and students to become better online learners and give them a solid understanding of what to prepare for and what to expect from future online classes. The kid-teach-kid learning model can significantly improve students' engagement in the online courses through the Project PWR to effectively supplement the traditional teacher-centric model that the Covid-19 pandemic has impacted substantially. Project PWR enables kids to share their interests and bond with one another, making the online learning environment effective and promoting positive and effective personal online one-on-one interactions.

Keywords: kid-teach-kid, affinity space, online learning, engagement, student-teacher

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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.

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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

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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

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

Abstract:

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

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Authors: Edith Kamakune

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As much as Indigenous rights are presumed to be part of the broad human rights regime, members of the indigenous communities have continually suffered violations, exclusions, and threat. There are a number of steps taken from the international community in trying to bridge the gap, and this has been through the inclusion of provisions as well as the passing of conventions and declarations with specific reference to the rights of indigenous peoples. Some examples of indigenous people include theSiberian Yupik of St Lawrence Island; the Ute of Utah; the Cree of Alberta, and the Xosa andKhoiKhoi of Southern Africa. Uganda’s wide cultural heritage has played a key role in the failure to pay special attention to the needs of the rights of indigenous peoples. The 1995 Constitution and the Land Act of 1998 provide for abstract land rights without necessarily paying attention to indigenous communities’ special needs. Basongora are a pastoralist community in Western Uganda whose ancestral land is the present Queen Elizabeth National Park of Western Uganda, Virunga National Park of Eastern Democratic Republic of Congo, and the small percentage of the low lands under the Rwenzori Mountains. Their values and livelihood are embedded in their strong attachment to the land, and this has been at stake for the last about 90 Years. This research was aimed atinvestigating the relationship between land rights and the right to cultural identity among indigenous communities, looking at the policy available on land and culture, and whether the policies are sensitive of the specific issues of vulnerable ethnic groups; and largely the effect of land on the right to cultural identity. The research was guided by three objectives: to examine and contextualize the concept of land rights among the Basongora community; to assess the policy frame work available for the protection of the Basongora community; to investigate the forms of vulnerability of the Basongora community. Quantitative and qualitative methods were used. a case of Kaseseand Kampala Districts were purposefully selected .138 people were recruited through random and nonrandom techniques to participate in the study, and these were 70 questionnaire respondents; 20 face to face interviews respondents; 5 key informants, and 43 participants in focus group discussions; The study established that Land is communally held and used and thatit continues to be a central source of livelihood for the Basongora; land rights are important in multiplication of herds; preservation, development, and promotion of culture and language. Research found gaps in the policy framework since the policies are concerned with tenure issues and the general provisions areambiguous. Oftenly, the Basongora are not called upon to participate in decision making processes, even on issues that affect them. The research findings call forauthorities to allow Basongora to access Queen Elizabeth National Park land for pasture during particular seasons of the year, especially during the dry seasons; land use policy; need for a clear alignment of the description of indigenous communitiesunder the constitution (Uganda, 1995) to the international definition.

Keywords: cultural identity, land rights, protection, uganda

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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

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Authors: Nurten Çelik

Abstract:

Under the new developments in science, medicine, sociology, psychology and literary theories, body studies has gained huge importance and the body has become a debatable issue. There has emerged, among sociologists and literary theorists, an overwhelming consensus that body is socially, politically and culturally perceived and constructed and thus, the position of an individual in the society is determined in accordance with his/her body image. In this regard, the most complicated point is the theoretical views propounded upon disability studies, where the disabled body is considered to be a site upon which social and political restrictions as well as repressions are inscribed. There has been the widely-accepted view that no matter what kind of disability it is, those with physical, mental or learning impairments face varied social, political and environmental obstacles that prevent them from being an active citizen, worker, lover and even a family member. In parallel with these approaches, the matter of the sufferings of disabled individuals attains its place in cinema and literature as well as in theatre studies under the category of disability theatre. One of the prominent plays that deal with physical disability came from the contemporary British playwright Nina Raine. In her awarded play Tribes, which premiered at the Royal Court Theatre in 2010, Raine develops the social strata where her deaf protagonist, Billy, caught up between two tribes – namely his family and his lover Slyvia, a member of the deaf community– experiences personal and social hardships due to his hearing impairment. In the play, intransigent and self-opinionated family members foster no sense of empathy towards Billy, there are noisy talking and shouting, but no communication, love, compassion or mutual understanding, and language becomes just a tool for the expression of rage and oppression. In the disordered atmosphere of the family life, Billy experiences isolation and loneliness. Billy’s hopes for success and love are destroyed when Slyvia, troubled between hearing and deafness, rejects him because she does not utterly grasp what Billy is experiencing. Drawing upon the hardships, Billy undergoes in his relationships with his family and his girlfriend, Tribes problematizes the concept of deafness and explores to what extent a deaf person can find a place in the hearing world. Setting ‘the disabled’ bodies against ‘the abled’ bodies in a family, a microcosm of the society where bodies are socially shaped and constructed, Tribes dramatizes how the disabled bodies are disenfranchised, stigmatised, marginalized and othered on the grounds that they are socially misfit. Tribes, with a specific focus on the dysfunctional family, shows that the lack of communication and empathy numbs the characters to the feelings of each other and thereby, they become more disabled than Billy. In conclusion, this paper, with the reference to the embodiment of disability and social theories, aims to explore how disabled bodies are socially marked and segregated from family and society.

Keywords: body, deafness, disability, disability theatre, Nina Raine, tribes

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Authors: Akanksha Agrawal, Richa Rathor, Geetha Suryakumar

Abstract:

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

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