Search results for: systemic rejection
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 899

Search results for: systemic rejection

809 Comparison Between Conventional Ultrafiltration Combined with Modified Ultrafiltration and Conventional Ultrafiltration Only for Adult Open-heart Surgery: Perspective from Systemic Inflammation, Vascular Resistance, and Cardiac Index

Authors: Ratna Farida Soenarto, Anas Alatas, Made Ryan Kharmayani

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Background: Conventional ultrafiltration (CUF) system was shown to be helpful in reducing anti-inflammatory mediators for patients who underwent open heart surgery. Additionally, modified ultrafiltration (MUF) has been shown to reduce anti-inflammatory mediators further while reducing interstitial fluid volume at the same time. However, there has been minimal data concerning the efficacy of combining both ultrafiltration methods. This study aims to compare inflammation marker, vascular resistance, and cardiac index on CUF+MUF patients with CUF only patients undergoing open heart surgery. Method: This is a single blind randomized controlled trial on patients undergoing open heart surgery between June 2021 - October 2021 in CiptoMangunkusumo National Referral Hospital and Jakarta Heart Hospital. Patients wererandomized using block randomization into modified ultrafiltration following conventional ultrafiltration (CUF+MUF) and conventional ultrafiltration (CUF) only. Outcome assessed in this study were 24-hoursinterleukin-6 levels, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), and cardiac index. Results: A total of 38patients were included (19 CUF+MUF and 19 CUF subjects). There was no difference in postoperative IL-6 level between groups (p > 0.05).No difference in PVR was observed between groups.Higher difference in SVR was observed in CUF+MUF group (-646 vs. -261dyn/s/cm-5, p < 0.05). Higher cardiac index was observed on CUF+MUF group (0.93 vs. 0.48, p < 0.05). Conclusion: Patients undergoing open heart surgery with modified ultrafiltration following conventional ultrafiltration had similar systemic inflammatory response and better cardiac response than those having conventional ultrafiltration.

Keywords: open-heart, CUF, MUF, SVR, PVR, IL-6

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808 Developing a Systemic Monoclonal Antibody Therapy for the Treatment of Large Burn Injuries

Authors: Alireza Hassanshahi, Xanthe Strudwick, Zlatko Kopecki, Allison J Cowin

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Studies have shown that Flightless (Flii) is elevated in human wounds, including burns, and reducing the level of Flii is a promising approach for improving wound repair and reducing scar formation. The most effective approach has been to neutralise Flii activity using localized, intradermal application of function blocking monoclonal antibodies. However, large surface area burns are difficult to treat by intradermal injection of therapeutics, so the aim of this study was to investigate if a systemic injection of a monoclonal antibody against Flii could improve healing in mice following burn injury. Flii neutralizing antibodies (FnAbs) were labelled with Alxa-Fluor-680 for biodistribution studies and the healing effects of systemically administered FnAbs to mice with burn injuries. A partial thickness, 7% (70mm2) total body surface area scald burn injury was created on the dorsal surface of mice (n=10/group), and 100µL of Alexa-Flour-680-labeled FnAbs were injected into the intraperitoneal cavity (IP) at time of injury. The burns were imaged on days 0, 1, 2, 3, 4, and 7 using IVIS Lumina S5 Imaging System, and healing was assessed macroscopically, histologically, and using immunohistochemistry. Fluorescent radiance efficiency measurements showed that IP injected Alexa-Fluor-680-FnAbs localized at the site of burn injury from day 1, remaining there for the whole 7-day study. The burns treated with FnAbs showed a reduction in macroscopic wound area and an increased rate of epithelialization compared to controls. Immunohistochemistry for NIMP-R14 showed a reduction in the inflammatory infiltrate, while CD31/VEGF staining showed improved angiogenesis post-systemic FnAb treatment. These results suggest that systemically administered FnAbs are active within the burn site and can improve healing outcomes. The clinical application of systemically injected Flii monoclonal antibodies could therefore be a potential approach for promoting the healing of large surface area burns immediately after injury.

Keywords: biodistribution, burn, flightless, systemic, fnAbs

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807 The Management of Behcet's Disease Patient's Mandibular Total Edentulism with Custom Made Implant Supported Bar Retainer: A Case Report

Authors: Faruk Emir, Simel Ayyıldız, Cem Şahin

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Behçet’s disease or Behçet’s syndrome is a chronic and multi-systemic inflammatory disease of unknown cause. This syndrome often presents with mucous membrane ulceration and ocular problems. As a systemic disease Behcet includes triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. Nearly all patients present with some form of painful oral mucocutaneous ulcerations in the form of aphthous ulcers. The aim of the treatment plan for Behçet’s Disease patients is to eliminate oral problems and increase the patient comfort.This clinical report represents the prosthodontic rehabilitation of Behcet’s disease patients mandibular total edentulism with the use of implant supported prosthesis that planned on custom abutments and bar retainers via CAD/CAM technology and patient satisfaction has been achieved in function and aesthetics.

Keywords: Behçet’s disease, CAD/CAM, custom-made manufacturing, titanium milled bar retainer

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806 Augmented ADRC for Trajectory Tracking of a Novel Hydraulic Spherical Motion Mechanism

Authors: Bin Bian, Liang Wang

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A hydraulic spherical motion mechanism (HSMM) is proposed. Unlike traditional systems using serial or parallel mechanisms for multi-DOF rotations, the HSMM is capable of implementing continuous 2-DOF rotational motions in a single joint without the intermediate transmission mechanisms. It has some advantages of compact structure, low inertia and high stiffness. However, as HSMM is a nonlinear and multivariable system, it is very complicate to realize accuracy control. Therefore, an augmented active disturbance rejection controller (ADRC) is proposed in this paper. Compared with the traditional PD control method, three compensation items, i.e., dynamics compensation term, disturbance compensation term and nonlinear error elimination term, are added into the proposed algorithm to improve the control performance. The ADRC algorithm aims at offsetting the effects of external disturbance and realizing accurate control. Euler angles are applied to describe the orientation of rotor. Lagrange equations are utilized to establish the dynamic model of the HSMM. The stability of this algorithm is validated with detailed derivation. Simulation model is formulated in Matlab/Simulink. The results show that the proposed control algorithm has better competence of trajectory tracking in the presence of uncertainties.

Keywords: hydraulic spherical motion mechanism, dynamic model, active disturbance rejection control, trajectory tracking

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805 The Mediator Role of Social Competence in the Relation between Effortful Control and Maths Achievement

Authors: M. A. Fernández-Vilar, M. D. Galián, E. Ato

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The aim of this work was to analyze the relation between children´s effortful control and Maths achievement in a sample of 447 Spanish children aged between 6 and 8 years. Traditionally, the literature confirms that higher level of effortful control has been associated with higher academic achievement, but there are few studies that include the effect that children´s social competence exert to this relation. To measure children’s effortful control parents were given the TMCQ (Temperament in Middle Childhood Questionnaire), and Maths achievement was taken from teacher´s rates. To measure social competence, we used the nominations method in the classroom context. Results confirmed that higher effortful control predicted a better maths achievement, whereas lower effortful control scores predicted lower Maths scores. Using a statistical modeling approach, we tested a mediation model that revealed the mediating role of social competence (popularity and rejection) in the relation between effortful control and Maths achievement. Concretely, higher social competence (higher popularity and lower rejection) seems to mediate the better Maths achievement showed by better self´regulated children. Therefore, an adequate social competence mediates the positive effect that self-regulatory capacity exerts to academic achievement. The clinical implications of the present findings should be considered. Specifically, rejected children must be detected and evaluated in community settings, such as school or community programs, due the relevant role of social competence in the relation between temperament and academic achievement.

Keywords: effortful control, maths achievement, social competence, mediation

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804 Suppression of Immunostimulatory Function of Dendritic Cells and Prolongation of Skin Allograft Survival by Dryocrassin

Authors: Hsin-Lien Lin, Ju-Hui Fu

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Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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803 A Critical Discourse Analysis of President Muhammad Buhari's Speeches

Authors: Joy Aworo-Okoroh

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Politics is about trust and trust is challenged by the speaker’s ability to manipulate language before the electorate. Critical discourse analysis investigates the role of language in constructing social relationships between a political speaker and his audience. This paper explores the linguistic choices made by President Muhammad Buhari that enshrines his ideologies as well as the socio-political relations of power between him and Nigerians in his speeches. Two speeches of President Buhari –inaugural and Independence Day speeches are analyzed using Norman Fairclough’s perspective on Halliday’s Systemic functional grammar. The analysis is at two levels. The first level of analysis is the identification of transitivity and modality choices in the speeches and how they reveal the covert ideologies. The second analysis is premised on Normal Fairclough’s model, the clauses are analyzed to identify elements of power, hesistation, persuasion, threat and religious statement. It was discovered that Buhari is a dominant character who manipulates the material processes a lot.

Keywords: politics, critical discourse analysis, Norman Fairclough, systemic functional grammar

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802 Rituximab Therapy for Musculoskeletal Involvement in Systemic Sclerosis

Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. There is very few data on changes of the musculoskeletal manifestations (artritis, arthralgia, muscle weakness, etc.) in systemic sclerosis (SSc) on rituximab (RTX) therapy. The aim of our study was to assess the severity of the musculoskeletal involvement in SSc patients (pts) and its changes during RTX therapy. Methods. Our study included 103 pts with SSc. The mean followup period was 12.6±10.7 months. The mean age was 47±12.9 years, female-87 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had interstitial lung disease (ILD) and were positive for ANA, 67% of them were positive for antitopoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. Arthritis was observed in 22 pts (21%), arthralgias in 47 pts (46%). Muscle weakness was observed in 17 pts (17%). Tendon friction rubs was established in 7 pts (7%). The results at baseline and at the end of the follow up are presented in the form of mean values. Results. There was an improvement of all outcome parameters and musculoskeletal manifestations on RTX therapy. There was a decrease in the number of pts with arthritis from 22 (21%) to 10 (9%), a decrease in the number of pts with arthralgias from 47 (46%) to 31 (30%). The number of pts with muscle weakness decreased from 17 (17%) to 7 (7%). The number of pts with tendon friction rubs decreased from 7 (7%) to 3 (3%). The creatine phosphokinase decreased from 365.5±186 to 70.8±50.4 (p=0.00006). The C-reactive protein (CRP) decreased from 23.2±31.3 to 8.62±7.4 (p=0.001). The dose of prednisolone was reduced from 11.3±4.5 to 9.8±3.5 mg/day (p=0.0004). Conclusion. In our study, musculoskeletal involvement was detected in almost half of the patients with SSc-ILD. There was an improvement of musculoskeletal manifestations despite a small cumulative dose of RTX. We also managed to reduce the dose of glucocorticosteroids. The improvement of musculoskeletal manifestations was accompanied by a decrease in laboratory parameters - creatine phosphokinase and CRP. RTX is effective option for treatment of musculoskeletal manifestations in SSc.

Keywords: arthritis, musculoskeletal involvement, systemic sclerosis, rituximab

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801 Shoulder-Arm Mobility and Upper and Lower Extremity Muscle Function are Impaired in Patients with Systemic Sclerosis

Authors: F. Bringby, A. Nordin, L. Björnådal, E. Svenungsson, C. Boström, H Alexanderson

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Patients with systemic sclerosis (SSc) have reduced hand function and self-reported limitations in daily activities. Few studies have explored limitations in shoulder-arm mobility and muscle function, or if there are differences in physical function between diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) SSc. The purpose of this study was to describe objectively assessed shoulder-arm mobility, lower extremity muscle function and muscle endurance in SSc and evaluate possible differences between lcSSc and dcSSc. 121 patients with SSc were included in this cross sectional study. Shoulder-arm mobility were examined using the Shoulder Function Assessment Scale (SFA) including 5 tasks ,lower extremity muscle function was measured by Timed stands test (TST) and muscle endurance in shoulder- and hip flexors were assessed by the Functional Index 2 (FI-2). Patients with dcSSc had median SFA hand to back score 5 (4-6) and median “hand to seat” score of 5 (4-6) compared to patients with lcSSc with corresponding median values of 6 (4-6) and 6 (5-6) respectively (p<0.01-p<0.05). 50% of both patientsgroups had lower muscle function assessed by the TST compared to age- and gender matched reference values but there were no differences in TST between the two patient groups. There was no difference in FI-2 scores between dcSSc and lcSSc. The whole group had 40 (28-83) % and 38 (32-72) % of maximal FI-2 shoulder flexion score on the right and left sides, and 40 (23-63) % and 37 (23-62) % of maximal FI-2 hip flexion score on the right and left sides. Reference values for the FI-2 indicate that healthy individuals perform in mean 100 % of maximal score. Patients with dcSSc were more limited than patients with lcSSc. Patients with SSc have reduced muscle function compared to reference values. These results highlights the importance of assessing shoulder-arm mobility and muscle function as well as a need for further research to identify exercise interventions to target these limitations.

Keywords: diffuse, limited, mobility, muscle function, physical therapy, systemic sclerosis

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800 Imidocloprid as a Systemic-Acquired Resistant (SAR) Inducer in Nicotiana tabacum Var. Samsun NN Infected with Tobacco Mild Green Mosaic Virus

Authors: Mohammad Reza Hossein Zadeh

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Plants have different layers of defense responses against biotic and abiotic stresses. One of the well-defined defense mechanism in plants is systemic acquired resistance (SAR) against a broad-range of pathogens. Salicylic acid (SA) plays a crucial role in regulation of the SAR pathway. It has been proved that Chemically SA-like compounds can mimic the SA signaling role. Imidocloprid is an insecticide being used to control whiteflies on crop plants. In order to study the possible role of Imidocloprid as an elicitor of SAR in plants, experiments were conducted in a completely randomized design frame with three treatments and duplicates on the detached leaves and whole Nicotiana tabacum var. Samsun NN. plants inoculated with Tobacco mild green mosaic virus (TMGMV). Compared with the effect of other SAR-inducers such as SA, Imidoclorid conferred a robust SAR induction in the infected plants. The results suggested that Imidocloprid even more powerful than SA can be considered as strong SAR inducer in the infected plants with viruses, which develop the local lesion symptoms.

Keywords: imidocloprid, Nicotiana tabacum var. Samsun NN, SAR, tobacco mild green, mosaic virus

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799 Identification of Potential Large Scale Floating Solar Sites in Peninsular Malaysia

Authors: Nur Iffika Ruslan, Ahmad Rosly Abbas, Munirah Stapah@Salleh, Nurfaziera Rahim

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Increased concerns and awareness of environmental hazards by fossil fuels burning for energy have become the major factor driving the transition toward green energy. It is expected that an additional of 2,000 MW of renewable energy is to be recorded from the renewable sources by 2025 following the implementation of Large Scale Solar projects in Peninsular Malaysia, including Large Scale Floating Solar projects. Floating Solar has better advantages over its landed counterparts such as the requirement for land acquisition is relatively insignificant. As part of the site selection process established by TNB Research Sdn. Bhd., a set of mandatory and rejection criteria has been developed in order to identify only sites that are feasible for the future development of Large Scale Floating Solar power plant. There are a total of 85 lakes and reservoirs identified within Peninsular Malaysia. Only lakes and reservoirs with a minimum surface area of 120 acres will be considered as potential sites for the development of Large Scale Floating Solar power plant. The result indicates a total of 10 potential Large Scale Floating Solar sites identified which are located in Selangor, Johor, Perak, Pulau Pinang, Perlis and Pahang. This paper will elaborate on the various mandatory and rejection criteria, as well as on the various site selection process required to identify potential (suitable) Large Scale Floating Solar sites in Peninsular Malaysia.

Keywords: Large Scale Floating Solar, Peninsular Malaysia, Potential Sites, Renewable Energy

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798 A Critical Discourse Analysis of Corporate Annual Reports in a Cross-Cultural Perspective: Views from Grammatical Metaphor and Systemic Functional Linguistics

Authors: Antonio Piga

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The study of language strategies in financial and corporate discourse has always been vital for understanding how companies manage to communicate effectively with a wider customer base and offers new perspectives on how companies interact with key stakeholders, not only to convey transparency and an image of trustworthiness, but also to create affiliation and attract investment. In the light of Systemic Functional Linguistics, the purpose of this study is to examine and analyse the annual reports of Asian and Western joint-stock companies involved in oil refining and power generation from the point of view of the functions and frequency of grammatical metaphors. More specifically, grammatical metaphor - through the lens of Critical Discourse Analysis (CDA) - is used as a theoretical tool for analysing a synchronic cross-cultural study of the communicative strategies adopted by Asian and Western companies to communicate social and environmental sustainability and showcase their ethical values, performance and competitiveness to local and global communities and key stakeholders. According to Systemic Functional Linguistics, grammatical metaphor can be divided into two broad areas: ideational and interpersonal. This study focuses on the first type, ideational grammatical metaphor (IGM), which includes de-adjectival and de-verbal nominalisation. The dominant and more effective grammatical tropes used by Asian and Western corporations in their annual reports were examined from both a qualitative and quantitative perspective. The aim was to categorise and explain how ideational grammatical metaphor is constructed cross-culturally and presented through structural language patterns involving re-mapping between semantics and lexico-grammatical features. The results show that although there seem to be more differences than similarities in terms of the categorisation of the ideational grammatical metaphors conceptualised in the two case studies analysed, there are more similarities than differences in terms of the occurrence, the congruence of process types and the role and function of IGM. Through the immediacy and essentialism of compacting and condensing information, IGM seems to be an important linguistic strategy adopted in the rhetoric of corporate annual reports, contributing to the ideologies and actions of companies to report and promote efficiency, profit and social and environmental sustainability, thus advocating the engagement and investment of key stakeholders.

Keywords: corporate annual reports, cross-cultural perspective, ideational grammatical metaphor, rhetoric, systemic functional linguistics

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797 Systemic Functional Linguistics in the Rhetorical Strategies of Persuasion: A Longitudinal Study of Transitivity and Ergativity in the Rhetoric of Saras’ Sustainability Reports

Authors: Antonio Piga

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This study explores the correlation between Systemic Functional Linguistics (SFL) and Critical Discourse Analysis (CDA) as tools for analysing the evolution of rhetoric in the communicative strategies adopted in a company’s Reports on social and environmental responsibility. In more specific terms, transitivity and ergativity- concepts from Systemic Functional Linguistics (SFL) - through the lenses of CDA, are employed as a theoretical means for the analysis of a longitudinal study in the communicative strategies employed by Saras SpA pre- and during the Covid-19 pandemic crisis. Saras is an Italian joint-stock company operating in oil refining and power generation. The qualitative and quantitative linguistic analysis carried out through the use of Sketch Engine software aims to identify and explain how rhetoric - and ideology - is constructed and presented through language use in Saras SpA Sustainability Reports. Specific focus is given to communication strategies to local and global communities and stakeholders in the years immediately before and during the Covid-19 pandemic. The rationale behind the study lies in the fact that 2020 and 2021 have been among the most difficult years since the end of World War II. Lives were abruptly turned upside down by the pandemic, which had grave negative effects on people’s health and on the economy. The result has been a threefold crisis involving health, the economy and social tension, with the refining sector being one of the hardest hit, since the oil refining industry was one of the most affected industries due to the general reduction in mobility and oil consumption brought about by the virus-fighting measures. Emphasis is placed on the construction of rhetorical strategies pre- and during the pandemic crisis using the representational process of transitivity and ergativity (SFL), thus revealing the close relationship between the use language in terms of Social Actors and semantic roles of syntactic transformation on the one hand, and ideological assumptions on the other. The results show that linguistic decisions regarding transitivity and ergativity choices play a crucial role in how effective writing achieves its rhetorical objectives in terms of spreading and maintaining dominant and implicit ideologies and underlying persuasive actions, and that some ideological motivation is perpetuated – if not actually overtly or subtly strengthened - in social-environmental Reports issued in the midst of the Covid-19 pandemic crisis.

Keywords: systemic functional linguistics, sustainability, critical discourse analysis, transitivity, ergativity

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796 Removal of Chromium by UF5kDa Membrane: Its Characterization, Optimization of Parameters, and Evaluation of Coefficients

Authors: Bharti Verma, Chandrajit Balomajumder

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Water pollution is escalated owing to industrialization and random ejection of one or more toxic heavy metal ions from the semiconductor industry, electroplating, metallurgical, mining, chemical manufacturing, tannery industries, etc., In semiconductor industry various kinds of chemicals in wafers preparation are used . Fluoride, toxic solvent, heavy metals, dyes and salts, suspended solids and chelating agents may be found in wastewater effluent of semiconductor manufacturing industry. Also in the chrome plating, in the electroplating industry, the effluent contains heavy amounts of Chromium. Since Cr(VI) is highly toxic, its exposure poses an acute risk of health. Also, its chronic exposure can even lead to mutagenesis and carcinogenesis. On the contrary, Cr (III) which is naturally occurring, is much less toxic than Cr(VI). Discharge limit of hexavalent chromium and trivalent chromium are 0.05 mg/L and 5 mg/L, respectively. There are numerous methods such as adsorption, chemical precipitation, membrane filtration, ion exchange, and electrochemical methods for the heavy metal removal. The present study focuses on the removal of Chromium ions by using flat sheet UF5kDa membrane. The Ultra filtration membrane process is operated above micro filtration membrane process. Thus separation achieved may be influenced due to the effect of Sieving and Donnan effect. Ultrafiltration is a promising method for the rejection of heavy metals like chromium, fluoride, cadmium, nickel, arsenic, etc. from effluent water. Benefits behind ultrafiltration process are that the operation is quite simple, the removal efficiency is high as compared to some other methods of removal and it is reliable. Polyamide membranes have been selected for the present study on rejection of Cr(VI) from feed solution. The objective of the current work is to examine the rejection of Cr(VI) from aqueous feed solutions by flat sheet UF5kDa membranes with different parameters such as pressure, feed concentration and pH of the feed. The experiments revealed that with increasing pressure, the removal efficiency of Cr(VI) is increased. Also, the effect of pH of feed solution, the initial dosage of chromium in the feed solution has been studied. The membrane has been characterized by FTIR, SEM and AFM before and after the run. The mass transfer coefficients have been estimated. Membrane transport parameters have been calculated and have been found to be in a good correlation with the applied model.

Keywords: heavy metal removal, membrane process, waste water treatment, ultrafiltration

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795 Contribution of mTOR to Oxidative/Nitrosative Stress via NADPH Oxidase System Activation in Zymosan-Induced Systemic Inflammation in Rats

Authors: Seyhan Sahan-Firat, Meryem Temiz-Resitoglu, Demet Sinem Guden, Sefika Pinar Kucukkavruk, Bahar Tunctan, Ayse Nihal Sari, Zumrut Kocak

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We hypothesized that mTOR inhibition may prevent the multiple organ failures following severe multiple tissue injury associated with increased NADPH oxidase system activity occur in zymosan-induced systemic inflammation. Therefore, we investigated the role of mTOR in oxidative/nitrosative stress associated with increase in NADPH oxidase activity in zymosan-induced systemic inflammation model in rats. Male Wistar rats received saline (4 ml/kg, i.p.) and zymosan (500 mg/kg, i.p.) at time 0. Saline, or zymosan-treated rats were given rapamycin (1 mg/kg, i.p.) 1 h after saline or zymosan injections. Rats were sacrified 4 h after zymosan challenge and kidney, heart, thoracic aorta, and superior mesenteric artery were collected. NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels were measured in tissue samples. Zymosan administration caused an increase in NADPH oxidase activity, p22phox, gp91phox, and p47phox protein expression and nitrotyrosine levels in kidney, heart, thoracic aorta, and superior mesenteric artery. These changes caused by zymosan reversed by rapamycin, a selective mTOR inhibitor. Rapamycin alone had no effect on the parameters measured. Our results demonstrated that zymosan-induced oxidative/nitrosative stress presumably due to enhanced activity of NADPH oxidase, expression of p22phox, gp91phox, and p47phox and production of peroxynitrite were mediated by mTOR. [This work was financially supported by Research Foundation of Mersin University (2016-2-AP3-1900)].

Keywords: oxidative stress, mTOR, nitrosative stress, zymosan

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794 Identification of Membrane Foulants in Direct Contact Membrane Distillation for the Treatment of Reject Brine

Authors: Shefaa Mansour, Hassan Arafat, Shadi Hasan

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Management of reverse osmosis (RO) brine has become a major area of research due to the environmental concerns associated with it. This study worked on studying the feasibility of the direct contact membrane distillation (DCMD) system in the treatment of this RO brine. The system displayed great potential in terms of its flux and salt rejection, where different operating conditions such as the feed temperature, feed salinity, feed and permeate flow rates were varied. The highest flux of 16.7 LMH was reported with a salt rejection of 99.5%. Although the DCMD has displayed potential of enhanced water recovery from highly saline solutions, one of the major drawbacks associated with the operation is the fouling of the membranes which impairs the system performance. An operational run of 77 hours for the treatment of RO brine of 56,500 ppm salinity was performed in order to investigate the impact of fouling of the membrane on the overall operation of the system over long time operations. Over this time period, the flux was observed to have reduced by four times its initial flux. The fouled membrane was characterized through different techniques for the identification of the organic and inorganic foulants that have deposited on the membrane surface. The Infrared Spectroscopy method (IR) was used to identify the organic foulants where SEM images displayed the surface characteristics of the membrane. As for the inorganic foulants, they were identified using X-ray Diffraction (XRD), Ion Chromatography (IC) and Energy Dispersive Spectroscopy (EDS). The major foulants found on the surface of the membrane were inorganic salts such as sodium chloride and calcium sulfate.

Keywords: brine treatment, membrane distillation, fouling, characterization

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793 Flying Women in Chinese Folklore – Male Narrator’s Rejection of Gender Role Division in Patriarchal Societies

Authors: Emma H. Zhang

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In Women Who Fly (2018), Serinity Young connects tales and legends of flying women in Greco-Roman, Indo-European, Mesopotamian, and Asian cultures with ancient matriarchal bird goddesses and argues that tales of flying women are reminiscent of the rituals and rites related to the worship of goddesses in pre-patriarchal times and that flying women, including swan maidens, harpies, fairies, and witches are “abnormal women” because they reject patriarchal order, defy, and desert their domestic roles. Tales of flying women in Chinese folklore, exemplified by the story of The Cowherd and the Weaver Girl, replicated in countless tales that depicts the courtship between a mortal man and a divine or magical woman suggest otherwise. In these tales, the divine woman exhibits idealized Confucian femininity and fulfills the needs of the male protagonist by providing him with marriage, children, social status, and financial affluence. This paper argues that the flying women in Chinese folklores are not a symbol of defiance but are exemplars that embodyideal Confucian femininity. These tales are instead a reflection of male rejection of gender division in patriarchal societies. The male protagonists, like the male storytellers, reject the necessity to pursue and provide for women in courtship and marriage. Though these tales show their authors’ and readers’ discontent with gender role division, they do not subvert the patriarchal social order but rather offers an escape through fantasy.

Keywords: bird goddess, folklore, gender role division, patriarchy

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792 Equipment Donation: A Perspective from a Teaching Tertiary Care Hospital in North India

Authors: Jitender Sodhi, Shweta Talati, A. K. Gupta, Pankaj Arora

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Background:Equipment donation to hospitals in resource-limited settings can significantly benefit services in these settings albeit requires important ethical, practical and financial issues to be considered before accepting donations. Objective: To understand the decision making process leading to acceptance/ rejection/ deferment of equipment donation from the perspective of a public sector teaching tertiary care hospital. Design: Retrospective, record based study. Setting: 2000-bedded public sector teaching tertiary care hospital in North India. Methods: A total of 30 cases of equipment donation from March 2010-October 2013, were analysed for their decision process leading to acceptance/rejection/deferment.Each case was studied retrospectively and data pertaining to the agenda and decision taken was collected. Results: A total of 30 cases of equipment donation received from March 2010- October 2013 were screened, out of which 17 (56.6%) were for diagnostic purpose and 13 (43.3%) for therapeutic purpose. Out of 30 cases, 16 (53.3%) were accepted and 8 (26.6%) were rejected. The remaining 6 cases included 3 (10%) which required further clarification and other 3 (10%) which were out of the domain of committee. Conclusion: This study highlights the importance of equipment donation in resource limited settings and considerations involved while making decisions for acceptance/rejections/defermentof such donations.

Keywords: equipment donation, teaching hospital, decision-making, North India

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791 Numerical Reproduction of Hemodynamic Change Induced by Acupuncture to ST-36

Authors: Takuya Suzuki, Atsushi Shirai, Takashi Seki

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Acupuncture therapy is one of the treatments in traditional Chinese medicine. Recently, some reports have shown the effectiveness of acupuncture. However, its full acceptance has been hindered by the lack of understanding on mechanism of the therapy. Acupuncture applied to Zusanli (ST-36) enhances blood flow volume in superior mesenteric artery (SMA), yielding peripheral vascular resistance – regulated blood flow of SMA dominated by the parasympathetic system and inhibition of sympathetic system. In this study, a lumped-parameter approximation model of blood flow in the systemic arteries was developed. This model was extremely simple, consisting of the aorta, carotid arteries, arteries of the four limbs and SMA, and their peripheral vascular resistances. Here, the individual artery was simplified to a tapered tube and the resistances were modelled by a linear resistance. We numerically investigated contribution of the peripheral vascular resistance of SMA to the systemic blood distribution using this model. In addition to the upstream end of the model, which correlates with the left ventricle, two types of boundary condition were applied; mean left ventricular pressure which correlates with blood pressure (BP) and mean cardiac output which corresponds to cardiac index (CI). We examined it to reproduce the experimentally obtained hemodynamic change, in terms of the ratio of the aforementioned hemodynamic parameters from their initial values before the acupuncture, by regulating the peripheral vascular resistances and the upstream boundary condition. First, only the peripheral vascular resistance of SMA was changed to show contribution of the resistance to the change in blood flow volume in SMA, expecting reproduction of the experimentally obtained change. It was found, however, this was not enough to reproduce the experimental result. Then, we also changed the resistances of the other arteries together with the value given at upstream boundary. Here, the resistances of the other arteries were changed simultaneously in the same amount. Consequently, we successfully reproduced the hemodynamic change to find that regulation of the upstream boundary condition to the value experimentally obtained after the stimulation is necessary for the reproduction, though statistically significant changes in BP and CI were not observed in the experiment. It is generally known that sympathetic and parasympathetic tones take part in regulation of whole the systemic circulation including the cardiac function. The present result indicates that stimulation to ST-36 could induce vasodilation of peripheral circulation of SMA and vasoconstriction of that of other arteries. In addition, it implies that experimentally obtained small changes in BP and CI induced by the acupuncture may be involved in the therapeutic response.

Keywords: acupuncture, hemodynamics, lumped-parameter approximation, modeling, systemic vascular resistance

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790 Differential Impact of Parenting on Mental Health Functioning of Pakistani Adolescents: A Cultural Perspective

Authors: Zahid Mahmood

Abstract:

Mental health problems in adolescents are said to be increasing tremendously, and a large proportion of adolescents are suffering from serious mental health problems that result in short and long term socio-emotional negative consequences. Contemporary clinical and school psychology is now focused on prevention rather than intervene in the mental health concerns of adolescents. Therefore, a wealth of literature is devoted to identify the risk and protective factors so that adolescents may be prevented and identified earlier. This quest has led to identify many risk factors including the early parent-child relationship. Parenting has a long last impact on the growth and development of an individual. If the parent-child relationship is secure and warm, the child tends to have a positive psychological outcome. On the other hand, if parenting is rejecting and distant, it may lead to more mental health problems. Keeping in view the cross-cultural influence of parenting, the current study was aimed to explore the relationship between parental rearing practices and mental health problems on a group of Pakistani adolescents. A sample of 805 participants (49% boys and 51% girls) were selected through a stratified sample with the age range of 13-18 years. All the participants were given protocol of EMBU-C and School Children Problem Scale (SCPS). Results indicate that age, the gender of the participant and parental rejection were found to be a significant positive predictor of mental health problems in adolescents. It can be concluded that parenting may be a universal phenomenon comprising rejection and acceptance yet the differential impact on mental health varies from culture to culture.

Keywords: parenting, mental health, adolescents, cross cultural

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789 Dual-Actuated Vibration Isolation Technology for a Rotary System’s Position Control on a Vibrating Frame: Disturbance Rejection and Active Damping

Authors: Kamand Bagherian, Nariman Niknejad

Abstract:

A vibration isolation technology for precise position control of a rotary system powered by two permanent magnet DC (PMDC) motors is proposed, where this system is mounted on an oscillatory frame. To achieve vibration isolation for this system, active damping and disturbance rejection (ADDR) technology is presented which introduces a cooperation of a main and an auxiliary PMDC, controlled by discrete-time sliding mode control (DTSMC) based schemes. The controller of the main actuator tracks a desired position and the auxiliary actuator simultaneously isolates the induced vibration, as its controller follows a torque trend. To determine this torque trend, a combination of two algorithms is introduced by the ADDR technology. The first torque-trend producing algorithm rejects the disturbance by counteracting the perturbation, estimated using a model-based observer. The second torque trend applies active variable damping to minimize the oscillation of the output shaft. In this practice, the presented technology is implemented on a rotary system with a pendulum attached, mounted on a linear actuator simulating an oscillation-transmitting structure. In addition, the obtained results illustrate the functionality of the proposed technology.

Keywords: active damping, discrete-time nonlinear controller, disturbance tracking algorithm, oscillation transmitting support, position control, stability robustness, vibration isolation

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788 Dwelling in the Built Environment: The Resilience by Design in Modular Thinking toward an Adaptive Alternatives

Authors: Tzen-Ying Ling

Abstract:

Recently, the resilience of dwellings in urban areas has been deliberated, as to accommodate the growing demand for changing the demography and rapid urbanization. The need to incorporate sustainability and cleaner production thinking have intensified to mitigate climate risks and satisfy the demand for housing. The modular thinking satisfies both the pressing call for fast-tracked housing stocks; while meeting the goal of more sustainable production. In the other side, the importance of the dwelling as a podium for well-being and social connectedness are sought to explore the key human/environment design thinking for the modular system in dwelling. We argue the best practice incorporates the concept of systemic components thinking. The fieldwork reported in this paper illustrates the process of the case study in a modular dwelling unit prototype development; focusing on the systemic frame system design process and adjustment recommendation hereafter. Using a case study method, the study identified that: (1) inclusive human dimensional factoring through systemic design thinking results in affordable implementations possibilities. (2) The environmental dimension encourages the place-based solution suited for the locality and the increasing demand for dwelling in the urban system. (3) Prototype design consideration avails module system component as dwelling construction alternative. (4) Building code often acts as an inhibitor for such dwelling units by the restriction in lot sizes and units placement. The demand for fast-track dwelling construction and cleaner production decisively outweighs the code inhibition; we further underscored the sustainability implication of the alternative prototype as the core of this study. The research suggests that modular thinking results in a resilient solution suited for the locality and the increasing demand for dwelling in the urban system.

Keywords: system prototype, urban resilience, human/environment dimension, modular thinking, dwelling alternative

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787 Discrete PID and Discrete State Feedback Control of a Brushed DC Motor

Authors: I. Valdez, J. Perdomo, M. Colindres, N. Castro

Abstract:

Today, digital servo systems are extensively used in industrial manufacturing processes, robotic applications, vehicles and other areas. In such control systems, control action is provided by digital controllers with different compensation algorithms, which are designed to meet specific requirements for a given application. Due to the constant search for optimization in industrial processes, it is of interest to design digital controllers that offer ease of realization, improved computational efficiency, affordable return rates, and ease of tuning that ultimately improve the performance of the controlled actuators. There is a vast range of options of compensation algorithms that could be used, although in the industry, most controllers used are based on a PID structure. This research article compares different types of digital compensators implemented in a servo system for DC motor position control. PID compensation is evaluated on its two most common architectures: PID position form (1 DOF), and PID speed form (2 DOF). State feedback algorithms are also evaluated, testing two modern control theory techniques: discrete state observer for non-measurable variables tracking, and a linear quadratic method which allows a compromise between the theoretical optimal control and the realization that most closely matches it. The compared control systems’ performance is evaluated through simulations in the Simulink platform, in which it is attempted to model accurately each of the system’s hardware components. The criteria by which the control systems are compared are reference tracking and disturbance rejection. In this investigation, it is considered that the accurate tracking of the reference signal for a position control system is particularly important because of the frequency and the suddenness in which the control signal could change in position control applications, while disturbance rejection is considered essential because the torque applied to the motor shaft due to sudden load changes can be modeled as a disturbance that must be rejected, ensuring reference tracking. Results show that 2 DOF PID controllers exhibit high performance in terms of the benchmarks mentioned, as long as they are properly tuned. As for controllers based on state feedback, due to the nature and the advantage which state space provides for modelling MIMO, it is expected that such controllers evince ease of tuning for disturbance rejection, assuming that the designer of such controllers is experienced. An in-depth multi-dimensional analysis of preliminary research results indicate that state feedback control method is more satisfactory, but PID control method exhibits easier implementation in most control applications.

Keywords: control, DC motor, discrete PID, discrete state feedback

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786 Enhance Customer Experience through Sustainable Development: The Case of a Natural Park

Authors: Lubica Hikkerova, Jean-Michel Sahut

Abstract:

This article aims to better understand how a natural park, with a touristic vocation, can benefit from its sustainable development approach to enhance the customer experience. For this aim, we analyze, on the one hand, the interactions between the different stakeholders in this sustainable tourism offer, their ways of cooperating to build this offer and, on the other hand, the perceptions of customers. To serve this purpose, two complementary qualitative methodologies have been conducted. As part of a systemic approach, a first study, through group discussions, was conducted with three categories of participants: (I) customers, (II) representatives of the park, communities, tourism offices and associations and 3-service providers in the park. For the second study, semi-directive interviews were realized with park managers and customers. Two levels of contributions have been found. First, we have demonstrated the value of a systemic approach to understanding sustainable tourism. Then, we developed, in the empirical part, a model of causal loops that allowed us to identify the various factors of the offer that decided potential tourists to visit the park and their impact on customer experience. The complementarity of this approach with semi-directive interviews with all the stakeholders enabled us to issue recommendations to improve the customer experience.

Keywords: sustainable tourism, systematic approach, price, park

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785 Comparative Evaluation of Seropositivity and Patterns Distribution Rates of the Anti-Nuclear Antibodies in the Diagnosis of Four Different Autoimmune Collagen Tissue Diseases

Authors: Recep Kesli, Onur Turkyilmaz, Cengiz Demir

Abstract:

Objective: Autoimmune collagen diseases occur with the immune reactions against the body’s own cell or tissues which cause inflammation and damage the tissues and organs. In this study, it was aimed to compare seropositivity rates and patterns of the anti-nuclear antibodies (ANA) in the diagnosis of four different autoimmune collagen tissue diseases (Rheumatoid Arthritis-RA, Systemic Lupus Erythematous-SLE, Scleroderma-SSc and Sjogren Syndrome-SS) with each other. Methods: One hundred eighty-eight patients applied to different clinics in Afyon Kocatepe University ANS Practice and Research Hospital between 11.07.2014 and 14.07.2015 that thought the different collagen disease such as RA, SLE, SSc and SS have participated in the study retrospectively. All the data obtained from the patients participated in the study were evaluated according to the included criteria. The historical archives belonging to the patients have been screened, assessed in terms of ANA positivity. The obtained data was analysed by using the descriptive statistics; chi-squared, Fischer's exact test. The evaluations were performed by SPSS 20.0 version and p < 0.05 level was considered as significant. Results: Distribution rates of the totally one hundred eighty-eight patients according to the diagnosis were found as follows: 82 (43.6%) were RA, 38 (20.2%) were SLE, 22 (11.7%) were SSc, and 46 (24.5%) were SS. Distribution of ANA positivity rates according to the collagen tissue diseases were found as follows; for RA were 54 (65,9 %), for SLE were 36 (94,7 %), for SSc were 18 (81,8 %), and for SS were 43 (93,5 %). Rheumatoid arthritis should be evaluated and classified as a different class among all the other investigated three autoimmune illnesses. ANA positivity rates were found as differently higher (91.5 %) in the SLE, SSc, and SS, from the RA (65.9 %). Differences at ANA positivity rates for RA and the other three diseases were found as statistically significant (p=0.015). Conclusions: Systemic autoimmune illnesses show broad spectrum. ANA positivity was found as an important predictor marker in the diagnosis of the rheumatologic illnesses. ANA positivity should be evaluated as more valuable and sensitive a predictor diagnostic marker in the laboratory findings of the SLE, SSc, and SS according to RA.

Keywords: antinuclear antibody (ANA), rheumatoid arthritis, scleroderma, Sjogren syndrome, systemic lupus Erythemotosus

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784 Popularization of Persian Scientific Articles in the Public Media: An Analysis Based on Experimental Meta-function View Point

Authors: Behnaz Zolfaghari

Abstract:

In civilized societies, linguists seek to find suitable equivalents for scientific terms in the common language of their society. Many researches have conducted surveys about language of science on one hand and media discourse on the other, but the goal of this research is the comparative analysis of science discourse in Persian academic media and public discourse in the general Persian media by applying experimental meta-function as one of the four theoretical tools introduced by Holiday’s Systemic Functional Grammar .The said analysis aims to explore the processes that can convert the language in which scientific facts are published to a language well suited to the interested layman. The results of comparison show that these two discourses use differently six processes of experimental meta-function. Comparing the redundancy of different processes, the researcher tried to re-identify these differences in these two discourses and present a model for the procedures of converting science discourse to popularized discourse. This model can be useful for those journalists and textbook authors who want to restate scientific technical texts in a simple style for inexpert addresser including general people and students.

Keywords: systemic functional grammar, discourse analysis, science language, popularization, media discourse

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783 Thin-Film Nanocomposite Membrane with Single-Walled Carbon Nanotubes Axial Positioning in Support Layer for Desalination of Water

Authors: Ahmed A. Alghamdi

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Single-walled carbon nanotubes (SWCNTs) are an outstanding material for applications in thermoelectric power generation, nanoelectronics, electrochemical energy storage, photovoltaics, and light emission. They are ultra-lightweight and possess electrical as well as thermal conductivity, flexibility, and mechanical strength. SWCNT is applicable in water treatment, brine desalination, removal of heavy metal ions associated with pollutants, and oil-water separation. Carbon nanotube (CNT) is believed to tackle the trade-off issue between permeability, selectivity, and fouling issues in membrane filtration applications. Studying these CNT structures, as well as their interconnection in nanotechnology, assists in finding the precise position to be placed for water desalination. Reverse osmosis (RO) has been used globally for desalination, resulting in purified water. Thin film composite (TFC) membranes were utilized in the RO process for desalination. The sheet thickness increases the salt rejection and decreases the water flux when CNT is utilized as a support layer to this membrane. Thus, through a temperature-induced phase separation technique (TIPS), axially aligned SWCNT (AASWCNT) is fabricated, and its use enhances the salt rejection and water flux at short reaction times with a modified procedure. An evaluation was conducted and analogized with prior works in the literature, which exhibited that the prepared TFC membrane showed a better outcome.

Keywords: single-walled carbon nanotubes, thin film composite, axially aligned swcnt, temperature induced phase separation technique, reverse osmosis

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782 Mood Choices and Modality Patterns in Donald Trump’s Inaugural Presidential Speech

Authors: Mary Titilayo Olowe

Abstract:

The controversies that trailed the political campaign and eventual choice of Donald Trump as the American president is so great that expectations are high as to what the content of his inaugural speech will portray. Given the fact that language is a dynamic vehicle of expressing intentions, the speech needs to be objectively assessed so as to access its content in the manner intended through the three strands of meaning postulated by the Systemic Functional Grammar (SFG): the ideational, the interpersonal and the textual. The focus of this paper, however, is on the interpersonal meaning which deals with how language exhibits social roles and relationship. This paper, therefore, attempts to analyse President Donald Trump’s inaugural speech to elicit interpersonal meaning in it. The analysis is done from the perspective of mood and modality which are housed in SFG. Results of the mood choice which is basically declarative, reveal an information-centered speech while the high option for the modal verb operator ‘will’ shows president Donald Trump’s ability to establish an equal and reliant relationship with his audience, i.e., the Americans. In conclusion, the appeal of the speech to different levels of Interpersonal meaning is largely responsible for its overall effectiveness. One can, therefore, understand the reason for the massive reaction it generates at the center of global discourse.

Keywords: interpersonal, modality, mood, systemic functional grammar

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781 Language and Power Relations in Selected Political Crisis Speeches in Nigeria: A Critical Discourse Analysis

Authors: Isaiah Ifeanyichukwu Agbo

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Human speech is capable of serving many purposes. Power and control are not always exercised overtly by linguistic acts, but maybe enacted and exercised in the myriad of taken-for-granted actions of everyday life. Domination, power control, discrimination and mind control exist in human speech and may lead to asymmetrical power relations. In discourse, there are persuasive and manipulative linguistic acts that serve to establish solidarity and identification with the 'we group' and polarize with the 'they group'. Political discourse is crafted to defend and promote the problematic narrative of outright controversial events in a nation’s history thereby sustaining domination, marginalization, manipulation, inequalities and injustices, often without the dominated and marginalized group being aware of them. They are designed and positioned to serve the political and social needs of the producers. Political crisis speeches in Nigeria, just like in other countries concentrate on positive self-image, de-legitimization of political opponents, reframing accusation to one’s advantage, redefining problematic terms and adopting reversal strategy. In most cases, the people are ignorant of the hidden ideological positions encoded in the text. Few researches have been conducted adopting the frameworks of critical discourse analysis and systemic functional linguistics to investigate this situation in the political crisis speeches in Nigeria. In this paper, we focus attention on the analyses of the linguistic, semantic, and ideological elements in selected political crisis speeches in Nigeria to investigate if they create and sustain unequal power relations and manipulative tendencies from the perspectives of Critical Discourse Analysis (CDA) and Systemic Functional Linguistics (SFL). Critical Discourse Analysis unpacks both opaque and transparent structural relationships of power dominance, power relations and control as manifested in language. Critical discourse analysis emerged from a critical theory of language study which sees the use of language as a form of social practice where social relations are reproduced or contested and different interests are served. Systemic function linguistics relates the structure of texts to their function. Fairclough’s model of CDA and Halliday’s systemic functional approach to language study are adopted in this paper. This paper probes into language use that perpetuates inequalities. This study demystifies the hidden implicature of the selected political crisis speeches and reveals the existence of information that is not made explicit in what the political actors actually say. The analysis further reveals the ideological configurations present in the texts. These ideological standpoints are the basis for naturalizing implicit ideologies and hegemonic influence in the texts. The analyses of the texts further uncovered the linguistic and discursive strategies deployed by text producers to manipulate the unsuspecting members of the public both mentally and conceptually in order to enact, sustain and maintain unhealthy power relations at crisis times in the Nigerian political history.

Keywords: critical discourse analysis, language, political crisis, power relations, systemic functional linguistics

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780 iPSC-derived MSC Mediated Immunosuppression during Mouse Airway Transplantation

Authors: Mohammad Afzal Khan, Fatimah Alanazi, Hala Abdalrahman Ahmed, Talal Shamma, Kilian Kelly, Mohammed A. Hammad, Abdullah O. Alawad, Abdullah Mohammed Assiri, Dieter Clemens Broering

Abstract:

Lung transplantation is a life-saving surgical replacement of diseased lungs in patients with end-stage respiratory malfunctions. Despite the remarkable short-term recovery, long-term lung survival continues to face several significant challenges, including chronic rejection and severe toxic side-effects due to global immunosuppression. Stem cell-based immunotherapy has been recognized as a crucial immunoregulatory regimen in various preclinical and clinical studies. Despite initial therapeutic outcomes, conventional stem cells face key limitations. The Cymerus™ manufacturing facilitates the production of a virtually limitless supply of consistent human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells, which could play a key role in selective immunosuppression and graft repair during rejection. Here, we demonstrated the impact of iPSC-derived human MSCs on the development of immune-tolerance and long-term graft survival in mouse orthotopic airway allografts. BALB/c→C57BL/6 allografts were reconstituted with iPSC-derived MSCs (2 million/transplant/ at d0), and allografts were examined for regulatory T cells (Tregs), oxygenation, microvascular blood flow, airway epithelium and collagen deposition during rejection. We demonstrated that iPSC-derived MSC treatment leads to significant increase in tissue expression of hTSG-6 protein, followed by an upregulation of mouse Tregs and IL-5, IL-10, IL-15 cytokines, which augments graft microvascular blood flow and oxygenation, and thereby maintained a healthy airway epithelium and prevented the subepithelial deposition of collagen at d90 post-transplantation. Collectively, these data confirmed that iPSC-derived MSC-mediated immunosuppression has potential to establish immune-tolerance and rescue allograft from sustained hypoxic/ischemic phase and subsequently limits long-term airway epithelial injury and collagen progression, which therapeutically warrant a study of Cymerus iPSC-derived MSCs as a potential management option for immunosuppression in transplant recipients.

Keywords: stem cell therapy, immunotolerance, regulatory T cells, hypoxia and ischemia, microvasculature

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