Search results for: TGF-β/CD4+CD25+Foxp3high T regulatory pathway

Authors: Ahmad Badawi Saluy

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This study aims to develop strategies for the prevention or elimination of environmental pollution as well as changes in external variables of the environment in order to implement the environmental management system ISO 14001:2004 by integrating analysis of environmental issues data, RKL-RPL transactional data and regulation as part of ERP on the management dashboard. This research uses a quantitative descriptive approach with analysis method comparing with air quality standard (PP 42/1999, LH 21/2008), water quality standard (permenkes RI 416/1990, KepmenLH 51/2004, kepmenLH 55/2013 ), and biodiversity indicators. Based on the research, the parameters of RPL monitoring have been identified, among others, the quality of emission air (SO₂, NO₂, dust, particulate) due to the influence of fuel quality, combustion performance in a combustor and the effect of development change around the generating area. While in water quality (TSS, TDS) there was an increase due to the flow of water in the cooling intake carrying sedimentation from the flow of Banjir Kanal Timur. Including compliance with the ISO 14001:2004 clause on application design significantly contributes to the improvement of the quality of power plant management.

Keywords: environmental management systems, power plant management, regulatory compliance , enterprises resource planning

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Authors: Josephine Mutwale-Ziko, Nonde Lushinga, Inonge Akakandelwa

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The study discusses the effectiveness of health and safety induction practices on construction sites against the background of the Zambian construction industry experience. The research design included the literature review of relevant literature. Questionnaires and interviews were administered to regulatory bodies, health, and safety personnel. Observation was also employed on construction sites to assess the health and safety practices being used. Health and safety in the construction industry are not something to be ignored or overlooked. The construction industry needs to take heed of the serious consequences of inadequate health and safety induction practices. The implications of inadequate health and safety induction procedures included among others threats to profitability, corporate social responsibility and increased turnover of the workforce leading to poor productivity. Adequate health and safety practices can improve the health and wellbeing of employees, reduce financial implications on firms and encourage productivity on construction sites. Despite this, accidents are still prevalent on construction sites in Zambia. The overall result of this research denotes that the implementation of health and safety induction practices is inadequate, as indicated by the negligent and non-adherent attitude to health and safety induction aspects on the sites by most stakeholders on construction sites. Therefore, health and safety induction practices are ineffective as preventive measures for reduction of accidents on construction sites in Zambia.

Keywords: accidents, health and safety, inadequate, induction

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Authors: A. Duncan, A. Blake, A. O'Gara, J. Fitzgerald

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Introduction: Acute traumatic rib fractures have significant morbidity and mortality and are a commonly seen injury in trauma patients. Rib fracture pain can often be acute and can prove challenging to manage. We performed an audit on patients with acute traumatic rib fractures with the aim of composing a referral and treatment pathway for such patients. Methods: From January 2021 to January 2022, the pain medicine service encouraged early referral of all traumatic rib fractures to the pain service for a multi-modal management approach. A retrospective audit of analgesic management was performed on a select cohort of 24 patients, with a mean age of 67, of which 19 had unilateral rib fractures. Results: 17 of 24 patients (71%) underwent local, regional block as part of a multi-modal analgesia regime. Only one regional complication was observed, seen with hypotension occurring in one patient with a thoracic epidural. The group who did not undergo regional block had a length of stay (LOS) 17 days longer than those who did (27 vs. 10) and higher rates of pneumonia (29% vs. 18%). Conclusion: Early referral to pain specialists is an important component of the effective management of acute traumatic rib fractures. From our audit, it is evident that regional blocks can be effectively used in these cases as part of a multi-modal analgesia regime and may confer benefits in terms of respiratory complications and length of stay.

Keywords: rib fractures, regional blocks, thoracic epidural, erector spina block

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Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

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Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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Authors: Saroj Poudel, Joshua Mancini, Douglas Pike, Jennifer Timm, Alexei Tyryshkin, Vikas Nanda, Paul Falkowski

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On the early Earth, protein-metal complexes likely harvested energy from a reduced environment. These complexes would have been precursors to the metabolic enzymes of ancient organisms. Hydrogenase is an essential enzyme in most anaerobic organisms for the reduction and oxidation of hydrogen in the environment and is likely one of the earliest evolved enzymes. To attempt to reinvent a precursor to modern hydrogenase, we computationally designed a short thirteen amino acid peptide that binds the often-required catalytic transition metal Nickel in hydrogenase. This simple complex can achieve hundreds of hydrogen evolution cycles using light energy in a broad range of temperature and pH. Biophysical and structural investigations strongly indicate the peptide forms a di-nickel active site analogous to Acetyl-CoA synthase, an ancient protein central to carbon reduction in the Wood-Ljungdahl pathway and capable of hydrogen evolution. This work demonstrates that prior to the complex evolution of multidomain enzymes, early peptide-metal complexes could have catalyzed energy transfer from the environment on the early Earth and enabled the evolution of modern metabolism

Keywords: hydrogenase, prebiotic enzyme, metalloenzyme, computational design

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Authors: Daniel C. Bonzo

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Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

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Authors: Anusha Bhardwaj, Shekhar Shinde

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Nitric oxide (NO•) has been documented in research papers as one of the most versatile player in the therapeutics. It is identified as a biological multifunctional messenger molecule which is synthesized by the action of nitric oxide synthase (NOS) enzyme from L-arginine. The protective and the toxic effect in conjunction form the complete picture of the biological function of nitric oxide in humans. The dual nature is because of various factors such as concentration of NO, the isoform of NOS involved, type of cells in which it is synthesized, reaction partners like proteins, reactive oxygen intermediates, prosthetic groups, thiols etc., availability of the substrate L-arginine, intracellular environment in which NO is produced and generation of guanosine 3, 5’- cyclic monophosphate (cGMP). Activation of NOS through infection or trauma leads to one or more systemic effects including enhanced immune activity against invading pathogens, vaso/bronchodilatation in the cardiovascular and respiratory systems and altered neurotransmission which can be protective or toxic. Hence, NO affects the balance between healthy signaling and neurodegeneration in the brain. In lungs, it has beneficial effects on the function of airways as a bronchodilator and acts as the neurotransmitter of bronchodilator nerves. Whereas, on the other hand, NO may have deleterious effects by amplifying the asthmatic inflammatory response and also act as a vasodilator in the airways by increasing plasma exudation. But NOS Inhibitors and NO donors hamper the signalling pathway and hence a therapeutic application of NO is compromised.

Keywords: nitric oxide, multifunctional, dual nature, therapeutic applications

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Authors: Abdelgawad, Salah El-Tahawy

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This paper aimed to establish econometrical equation models for the Nile delta region in Egypt, which will represent a basement for future predictions of Lumpy skin disease outbreaks and its pathway in relation to climate change. Data of lumpy skin disease (LSD) outbreaks were collected from the cattle farms located in the provinces representing the Nile delta region during 1 January, 2015 to December, 2015. The obtained results indicated that there was a significant association between the degree of the LSD outbreaks and the investigated climate factors (temperature, wind speed, and humidity) and the outbreaks peaked during the months of June, July, and August and gradually decreased to the lowest rate in January, February, and December. The model obtained depicted that the increment of these climate factors were associated with evidently increment on LSD outbreaks on the Nile Delta of Egypt. The model validation process was done by the root mean square error (RMSE) and means bias (MB) which compared the number of LSD outbreaks expected with the number of observed outbreaks and estimated the confidence level of the model. The value of RMSE was 1.38% and MB was 99.50% confirming that this established model described the current association between the LSD outbreaks and the change on climate factors and also can be used as a base for predicting the of LSD outbreaks depending on the climatic change on the future.

Keywords: LSD, climate factors, Nile delta, modeling

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Authors: Kishor P. Kadam

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Foreign direct investment policy (FDI) is defined as an investment involving a long term relationship and reflecting a long duration interest and control of a resident entity in the home country (foreign direct investor or parent firm) in the host country. India has been one of the most translucent and open-minded FDI regimes among the emerging and developing economies. There is clear cut mentioned about the sectoral caps for foreign investment. The policy problems that have been identified by time to time surveys as acting as additional hurdles for FDI are laws, regulatory systems and government monopolies that do not have contemporary relevance. Foreign investment policies in the post-reforms period have emphasized greater encouragement and mobilization of non-debt creating private inflows for plunging reliance on debt flows. This paper will focus on how foreign direct investment policy changed from 1990-91 up to now. A time series data of 25 years is used for analysing the policy changes. It is observed that India has more liberal policy. The growth in number of Greenfield investments in India has been more impressive than the number of M&A deals whereas equity capital for incorporated bodies FDI inflows has been increased continuously 2014-15. India has made major changes in FDI Policy, and it has positive impact on economic development.

Keywords: FDI, India, economic development, government

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Authors: Abdulhameed Babatunde Owolabi, Benyoh Emmanuel Kigha Nsafon, Jeung-Soo Huh

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Energy efficiency measures for residential buildings in South Korea is a national issue because most of the apartments built in the last decades were constructed without proper energy efficiency measures making the energy performance of old buildings to be very poor when compared with new buildings. However, the adoption of advanced building technologies and regulatory building codes are effective energy efficiency strategies for new construction. There is a need to retrofits the existing building using energy conservation measures (ECMs) equipment’s in order to conserve energy and reduce GHGs emissions. To achieve this, the Institute for Global Climate Change and Energy (IGCCE), Kyungpook National University (KNU), Daegu, South Korea employed RETScreen Expert software to carry out measurement and verification (M&V) analysis on an existing building in Korea by using six years gas consumption data collected from Daesung Energy Co., Ltd in order to determine the building energy performance after the introduction of ECM. Through the M&V, energy efficiency is attained, and the resident doubt was reduced. From the analysis, a total of 657 Giga Joules (GJ) of liquefied natural gas (LNG) was consumed at the rate of 0.34 GJ/day having a peak in the year 2015, which cost the occupant the sum of $10,821.

Keywords: energy efficiency, measurement and verification, performance analysis, RETScreen experts

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Authors: D. D. Nguyen, H. S. Park, S. W. Yang, B. Thusa, Y. M. Kim, T. H. Lee

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Currently, the design response spectrum (i.e., Nuclear Regulatory Commission - NRC 1.60 spectrum) with the peak ground acceleration (PGA) 0.3g (for Safe Shutdown Earthquake level) is specified for designing the new nuclear power plant (NPP) structures in Korea. However, the recent earthquakes in the region such as the 2016 Gyeongju and the 2017 Pohang earthquake showed that the possible PGA of ground motions can be larger than 0.3g. Therefore, there is a need to analyze the seismic performance of the existing NPP structures under these earthquakes. An NPP model, APR-1400, which is designed and built in Korea was selected for a case study. The NPP structure is numerically modeled in terms of lumped-mass stick elements using OpenSees framework. The floor acceleration and displacement of components are measured to quantify the responses of components. The numerical results show that the floor spectral accelerations are significantly amplified in the components subjected to Korean earthquakes. A comparison between floor response spectra of Korean earthquakes and the NRC design motion highlights that the seismic design level of NPP components under an earthquake should be thoroughly reconsidered. Additionally, a seismic safety assessment of the equipment and relays attached to main structures is also required.

Keywords: nuclear power plant, floor response spectra, Korean earthquake, NRC spectrum

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Authors: Libena Cernohorska, Barbora Sutorova, Petr Teply

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There are pending discussions over an impact of global regulatory efforts on banks. In this paper we present a literature review on the profitability-risk-capital relationship in banking. Research papers dealing with this topic can be divided into two groups: the first group focusing on a capital-risk relationship and the second group analyzing a capital-profitability relationship. The first group investigates whether the imposition of stricter capital requirements reduces risk-taking incentives of banks based on a simultaneous equations model. Their model pioneered the idea that the changes in both capital and risk have endogenous and exogenous components. The results obtained by the authors indicate that changes in the capital level are positively related to the changes in asset risk. The second group of the literature concentrating solely on the relationship between the level of held capital and bank profitability is limited. Nevertheless, there are a lot of studies dealing with the banks’ profitability as such, where bank capital is very often included as an explanatory variable. Based on the literature review of dozens of relevant papers in this study, an empirical research on banks’ profitability and risk adjustment decisions under new banking rules Basel III rules can be easily undertaken.

Keywords: bank, Basel III, capital, decision making, profitability, risk, simultaneous equations model

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Authors: Hadia Abdel Aziz, Raghda El Ebrashi

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Business models are shaped by their design space or the environment they are designed to be implemented in. The rapidly changing economic, technological, political, regulatory and market external environment severely affects business logic. This is particularly true for social enterprises whose core mission is to transform their environments, and thus, their whole business logic revolves around the interchange between the enterprise and the environment. The context in which social business operates imposes different business design constraints while at the same time, open up new design opportunities. It is also affected to a great extent by the impact that successful enterprises generate; a continuous loop of interaction that needs to be managed through a dynamic capability in order to generate a lasting powerful impact. This conceptual research synthesizes and analyzes literature on social enterprise, social enterprise business models, business model innovation, business model design, and the open system view theory to propose a new business model design process for social enterprises that takes into account the critical role of environmental factors. This process would help the social enterprise develop a dynamic capability that ensures the alignment of its business model to its environmental context, thus, maximizing its probability of success.

Keywords: social enterprise, business model, business model design, business model environment

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Authors: Joeri N. Aulman

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In the remote Indian region of Gulbarga a case study of lean airport infrastructure development is getting ‘cast in stone’; In April the first turbo-props will land, and the optimized terminal building will process its first passengers, using minimal square meters in a facility that is based on a complete dress-down of the core operational processes. Yet the solution that resulted from this case study has such elegance in its simplicity that it has emboldened the local administration to invest in its construction and thus secure this remote region’s connectivity to India’s growth story. This paper aims to provide further background to the Gulbarga case study and its relevance to remote region connectivity, covering the demand that was identified, its practical application and its regulatory context and relevance for today’s airport manager and local administrators. This embodies the scope of the paper. In summary, the paper will give airport managers and regional authorities an overview and background to innovative case studies of lean airport infrastructure developments which combine both optimized CAPEX and running costs/OPEX without losing sight of the aspirational nature of up and coming remote regions; a truly sustainable model.

Keywords: airport, CAPEX, lean, sustainable, air connectivity, remote regions

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Authors: Khairy M. A. Zoheir

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One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid was investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells, and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid treated mice showed a significant decrease in the Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also down regulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs also found to be significantly upregulated in lipoic acid treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for therapy Rheumatoid arthritis.

Keywords: lipoic acid, chemokines, inflammatory, rheumatoid arthritis

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Authors: Anurag Kumar Pandey, Tapan Kumar Nath, Santanu Dhara

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Polluted water by industrial effluents or dyes has become a major global concern, particularly in developing countries. Such environmental contaminants constitute a serious threat to biodiversity, ecosystems, and human health worldwide; thus, their treatment is critical. The usage of nanoparticles has been discovered to be a potential water treatment method with high efficiency, cheap manufacturing costs, and green synthesis. Carbon dots have attracted the interest of researchers due to their unique properties, such as high water solubility, ease of production, great electron-donating ability, and low toxicity. In this context, we synthesized iodine-doped clove buds-derived carbon dots (I-CCDs) for the Fenton-like degradation of environmental contaminants in water (such as methylene blue (MB) and rhodamine-B (Rh-B) dye). The formation of I-CCDs has been confirmed using various spectroscopy techniques. I-CCDs have demonstrated remarkable optical, cytocompatibility, and antibacterial capabilities. The C-dots that were synthesized were found to be an effective catalyst for the reduction of MB and Rh-B utilizing NaBH4 as a reducing agent. UV-visible spectroscopy was used to construct a detailed pathway for dye reduction step by step. As-prepared I-CCDs have the potential to be a promising solution for wastewater purification and treatment systems.

Keywords: iodine-doped carbon dots, wastewater treatment and purification, environmental friendly, antibacterial

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Authors: Leila Alidokht

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PFAS (poly- and perfluoroalkyl substances) are a large collection of environmentally persistent organic chemicals of industrial origin that have a negative influence on human health and ecosystems. Many distinct PFAS are being utilized in a wide range of applications (on the order of thousands), and there is no comprehensive source of information on the many different compounds and their roles in diverse applications. Facilities are increasingly looking into ways to reduce waste from cleanup projects. PFAS are widespread in the environment, have been found in a wide range of human biomonitoring investigations, and are a rising source of regulatory concern for federal, state, and local governments. Nanotechnology has the potential to contribute considerably to the creation of a cleaner, greener technologies with considerable environmental and health benefits. Nanotechnology approaches are being studied for their potential to provide pollution management and mitigation options, as well as to increase the effectiveness of standard environmental cleanup procedures. Diversified nanoparticles have shown useful in removing certain pollutants from their original environment, such as sewage spills and landmines. Furthermore, they have a low hazardous effect during production rates and can thus be thoroughly explored in the future to make them more compatible with lower production costs.

Keywords: PFOS, PFOA, PFAS, soil remediation

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Authors: Eugene Stepanov, Arkadi Ponossov

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Ordinary differential equations with switching nonlinearities constitute a very useful tool in many applications. The solutions of such equations can usually be calculated analytically if they cross the discontinuities transversally. Otherwise, one has trajectories that slides along the discontinuity, and the calculations become less straightforward in this case. For instance, one of the problems one faces is non-uniqueness of the sliding modes. In the presentation, it is proposed to apply the theory of hybrid dynamical systems to calculate the solutions that are ‘hidden’ in the discontinuities. Roughly, one equips the underlying switched system with an explicitly designed discrete dynamical system (‘automaton’), which governs the dynamics of the switched system. This construction ‘splits’ the dynamics, which, as it is shown in the presentation, gives uniqueness of the resulting hybrid trajectories and at the same time provides explicit formulae for them. Projecting the hybrid trajectories back onto the original continuous system explains non-uniqueness of its trajectories. The automaton is designed with the help of the attractors of the specially constructed adjoint dynamical system. Several examples are provided in the presentation, which supports the efficiency of the suggested scheme. The method can be of interest in control theory, gene regulatory networks, neural field models and other fields, where switched dynamics is a part of the analysis.

Keywords: hybrid dynamical systems, singular perturbation analysis, sliding modes, switched dynamics

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Authors: Eteri Kharaishvili, Marina Chavleishvili, Manana Lobzhanidze, Nino Grigolia

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The article analyzes Georgia's involvement in global migration processes, assessing migration research and policy regulatory documents. The socio-economic situation of young people has been studied in the paper, their employment and unemployment levels are analyzed, reasons for migration of youth are revealed, the impact of migration on the socio-economic development of the country is substantiated. Youth demand on education is also assessed, problems in the education sector are identified, educational migration indicators are analyzed according to the internationalization process of this sector. Based on the analysis of the motivations of young people in Georgia, orientation of values and the aspects conditioning life strategies the factors affecting educational migration are determined and the results of the positive and negative impact of educational migration on the socio-economic development of the country are substantiated. The importance of efficient management of educational migration for Georgia in getting closer to the EU and achieving inclusive economic grow this substantiated. Recommendations for efficient management of the process of Georgian citizens’ learning and acquiring experience, as well as the internationalization of education sector and educational migration, are drawn.

Keywords: educational migration, migration management, migration of youth, socio-economic results of educational migration, youth employment

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Authors: Thomas P. Jones

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Overview: Drowning is an important cause of accidental death, particularly in children and young people. Although many survive drowning incidents, it is a relatively rare presenting complaint in Emergency Departments. When cases do present, they can be complex and unpredictable. For patients to receive the best care, it is important that their management is standardized and evidence based, however this can be difficult in a topic area with limited studies and inconsistencies in case reporting. Objectives: To review recent cases to assess the performance of Manchester Royal Infirmary Emergency Department in the management of near drowning. To produce evidence based guideline on the management of drowning victims in the ED. Methods: Emergency department records were searched for patients with the diagnosis of ‘fatal drowning’ or ‘nearly drowning’ and two relevant case notes reviewed. To produce the guideline a literature review was conducted and a series of structured short cut systematic reviews known as Best BETs carried out. This information was used to produce a clear treatment pathway. Results: The case studies emphasized the variety in presentation of drowning victims whilst highlighting inconsistencies in management and documentation. An evidence-based guideline is presented as a flowchart, which illustrates the relevant investigations and treatment that victims of a drowning incident should receive, based on the best available evidence. Conclusion: It is hoped that when put into practice, the guideline will improve and standardize patient care in cases of near drowning. An audit is recommended to assess its effectiveness.

Keywords: drowning, near drowning, non fatal drowning, fatal drowning

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Authors: Lorena F. Axinte

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Territorial rescaling is a universal practice in the UK, following a logic of agglomeration and competition as the only chance for cities to thrive. Cardiff Capital Region is one of the latest examples, and its governance structures and developmental narratives are currently being shaped. Its evolution must be compatible with the Wellbeing of Future Generations Act, a Welsh legislation that requires public bodies to put sustainability at the core of all actions. Departing from this case study, the project follows the evolution of Cardiff Capital Region and assesses it based on a new a conceptual framework that connects the notions of regenerative development, collaborative governance, and progressive regionalism. The hypothetical synergies between these different theoretical perspectives are demonstrated, inferring that if regenerative development is aimed at, it must necessarily start with collaborative modes of governance. The objective is to explore (a) whether expanding the network of active stakeholders who get to intervene in the governance structure can contribute to a more progressive definition and development of the city region and (b) whether this can be considered a pathway towards regenerative development. The exploratory fieldwork conducted during the initial phase of the project used qualitative methods, which will be complemented next by different participatory research approaches, as well as a quantitative analysis. Despite being in its early days, the study is showing that a wider range of voices can indeed change priorities, reconcile and balance between the economic drivers and the wider social, economic, cultural and environmental aspects.

Keywords: Cardiff Capital Region, collaborative governance, progressive regionalism, regenerative development

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Authors: Raphaël Weuts, Mykyta Petik, Anton Vedder

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Artificial Intelligence has the potential to create and already creates enormous value in healthcare. Prescriptive systems might be able to make the use of healthcare capacity more efficient. Such systems might entail interpretations that exclude the effect of confounders that brings risks with it. Those risks might be mitigated by regulation that prevents systems entailing such risks to come to market. One modality of regulation is that of legislation, and the European AI Act is an example of such a regulatory instrument that might mitigate these risks. To assess the risk mitigation potential of the AI Act for those risks, this research focusses on a case study of a hypothetical application of medical device software that entails the aforementioned risks. The AI Act refers to the harmonised norms for already existing legislation, here being the European medical device regulation. The issue at hand is a causal link between a confounder and the value the algorithm optimises for by proxy. The research identifies where the AI Act already looks at confounders (i.a. feedback loops in systems that continue to learn after being placed on the market). The research identifies where the current proposal by parliament leaves legal uncertainty on the necessity to check for confounders that do not influence the input of the system, when the system does not continue to learn after being placed on the market. The authors propose an amendment to article 15 of the AI Act that would require high-risk systems to be developed in such a way as to mitigate risks from those aforementioned confounders.

Keywords: AI Act, healthcare, confounders, risks

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Authors: Swapna Guntupalli, Leela Madhuri Chalasani, Kshatri Jyothi, C. V. Rao, Bondili J. S.

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The study hypothesizes that enhanced biodegradation of Polycyclic Aromatic Hydrocarbons (PAHs) is achievable with an assemblage of microorganisms that are capable of producing biofilm and biosurfactants. Accordingly, PAHs degrading microorganism’s (bacteria, fungi, actinomycetes and yeast) were screened and grouped into different consortia based on their capabilities to produce biofilm and biosurfactants. Among these, Consortium BTSN09 consisting of bacterial fungal cocultures showed highest degradation due to the synergistic action between them. Degradation effiencies were evaluated using HPLC and GC-MS. Within 7days, BTSN09 showed 51% and 50.7% degradation of Phenanthrene (PHE) and Pyrene (PYR) with 200mg/L and 100 mg/L concentrations respectively in a liquid medium. In addition, several degradative enzymes like laccases, 1hydroxy-2-naphthoicacid dioxygenase, 2-carboxybenzaldehyde dehydrogenase, catechol1,2 dioxygenase and catechol2,3 dioxygenase activity was observed during degradation. Degradation metabolites were identified using GC-MS analysis and from the results it was confirmed that the metabolism of degradation proceeds via pthalic acid pathway for both PAHs. Besides, Microbial consortia also demonstrated good biosurfactant production capacity, achieving maximum oil displacement area and emulsification activity of 19.62 cm2, 65.5% in presence of PAHs as sole carbon source. Scanning Electron Microscopy analysis revealed exopolysaccharides (EPS) production, micro and macrocolonies formation with different stages of biofim development in presence of PAHs during degradation.

Keywords: PAHs, biosurfactant, biofilm, biodegradation

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Authors: Usha Kiran, M. Z. Abdin

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Osmotin is an abundant cationic multifunctional protein discovered in cells of tobacco (Nicotiana tabacum L. var Wisconsin 38) adapted to an environment of low osmotic potential. It provides plants protection from pathogens, hence placed in the PRP family of proteins. The osmotin induced proline accumulation has been reported in plants including transgenic tomato and strawberry conferring tolerance against both biotic and abiotic stresses. The exact mechanism of induction of proline by osmotin is however, not known till date. These observations have led us to hypothesize that osmotin induced proline accumulation could be due to its involvement as transcription factor and/or cell signal pathway modulator in proline biosynthesis. The present investigation was therefore, undertaken to analyze the osmotin protein as transcription factor /cell signalling modulator using bioinformatics tools. The results of available online DNA binding motif search programs revealed that osmotin does not contain DNA-binding motifs. The alignment results of osmotin protein with the protein sequence from DATF showed the homology in the range of 0-20%, suggesting that it might not contain a DNA binding motif. Further to find unique DNA-binding domain, the superimposition of osmotin 3D structure on modeled Arabidopsis transcription factors using Chimera also suggested absence of the same. We, however, found evidence implicating osmotin in cell signaling. With these results, we concluded that osmotin is not a transcription factor but regulating proline biosynthesis and accumulation through cell signaling during abiotic stresses.

Keywords: osmotin, cell signaling modulator, bioinformatic tools, protein

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Authors: Janneth Gonzalez, Marco Avila, George Barreto

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GRP78 participates in multiple functions in the cell during normal and pathological conditions, controlling calcium homeostasis, protein folding and unfolded protein response. GRP78 is located in the endoplasmic reticulum, but it can change its location under stress, hypoxic and apoptotic conditions. NF-κB represents the keystone of the inflammatory process and regulates the transcription of several genes related with apoptosis, differentiation, and cell growth. The possible relationship between GRP78-NF-κB could support and explain several mechanisms that may regulate a variety of cell functions, especially following brain injuries. Although several reports show interactions between NF-κB and heat shock proteins family members, there is a lack of information on how GRP78 may be interacting with NF-κB, and possibly regulating its downstream activation. Therefore, we assessed the computational predictions of the GRP78 (Chain A) and NF-κB complex (IkB alpha and p65) protein-protein interactions. The interaction interface of the docking model showed that the amino acids ASN 47, GLU 215, GLY 403 of GRP78 and THR 54, ASN 182 and HIS 184 of NF-κB are key residues involved in the docking. The electrostatic field between GRP78-NF-κB interfaces and molecular dynamic simulations support the possible interaction between the proteins. In conclusion, this work shed some light in the possible GRP78-NF-κB complex indicating key residues in this crosstalk, which may be used as an input for better drug design strategy targeting NF-κB downstream signaling as a new therapeutic approach following brain injuries.

Keywords: computational biology, protein interactions, Grp78, bioinformatics, molecular dynamics

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Authors: Khairy Mohamed Abdalla Zoheir

Abstract:

One of the most severe complications of Rheumatoid arthritis is delayed recovery. lipoic acid possesses antioxidant, hypoglycemic, and anti-inflammatory activity. In the present study, the effects of lipoic acid were investigated on the key mediators of Rheumatoid arthritis, namely, CD4+CD25+ T cell subsets, GITR expressing cells, CD4+CD25+Foxp3+ regulatory T (Treg) cells, T-helper-17 (Th17) cells and pro-inflammatory cytokines Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Tumor Necrosis Factor- α (TNF-α)] through flow-cytometry and qPCR analyses. Lipoic acid-treated mice showed a significant decrease in Rheumatoid arthritis, the frequency of GITR-expressing cells, and Th1 cytokines (IL-17A, TNF-αand Interferon- γ (IFN-γ) compared with positive and negative controlled mice. Lipoic acid treatment also downregulated the mRNA expression of the inflammatory mediators compared with the Rheumatoid arthritis mouse model and untreated mice. The number of Tregs was also found to be significantly upregulated in lipoic acid-treated mice. Our results were confirmed by the histopathological examination. This study showed the beneficial role of lipoic acid in promoting a well-balanced tool for the therapy of Rheumatoid arthritis.

Keywords: lipoic acid, inflammatory markers, rheumatoid arthritis, qPCR

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Authors: H. Fraga, J. A. Santos

Abstract:

Vitiviniculture in Portugal is a key socio-economic sector, with a strong connection to local traditions and culture. Despite being a relatively small country, with prevailing Mediterranean environments, Portugal comprises an exceptionally large diversity of growth conditions (Terroirs). The vineyard area in Portugal is over 190 thousand hectares, being the eleventh wine producer and ninth wine exporter worldwide. Owing to the strong impact of weather and climate conditions on grapevine physiological development, grape berry quantity and quality show important inter-annual variability. Grapevines are also susceptible to climate change, as their responses will be unavoidably different under future climates. These impacts may change wine typicity of a given region or even its viticultural suitability. The current study reveals that the projected warming and drying trends for Portugal under the Representative Concentration Pathway (RCP) 4.5 and 8.5, are projected to 1) significantly shift current grapevine growing thermal conditions (e.g., heat and chill accumulation), 2) enhance water stress, 3) anticipate phenological timings and 4) modify yields. Moreover, the present study provides some hints regarding the effectiveness of mulching and irrigation as climate change adaptation measures. Our results show that the effectiveness of these adaptation measures will strongly rest on the strength of the climate change signal at a local scale, thus emphasizing the need for local-to-regional climate change assessments.

Keywords: viticulture, climate change, adaptation measures, Portugal

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: Amir Shafiq, Asif Shahzad, Shabbar Mehmood, Muhammad Saeed, Hamid Mustafa

Abstract:

Legislation includes the law or the statutes which is being reputable by a sovereign authority and generally can be implemented by the courts of law time to time to accomplish the objectives. Historically speaking upon the emergence of Pakistan in 1947, the intact laws of the British Raj remained effective after ablution by Islamic Ideology. Thus, there was an intention to begin the statutes book afresh for Pakistan's legal history. In consequence thereof, the process of developing detailed plans, procedures and mechanisms to ensure legislative and regulatory requirements are achieved began keeping in view the cultural values and the local customs. This article is an input to the enduring discussion about implementing rule of law in Pakistan whereas; the rule of law requires the harmony of laws which is mostly in the arrangement of codified state laws. Pakistan has legal plural civilizations where completely different and independent systems of law like the Mohammadan law, the state law and the traditional law exist. The prevailing practiced law in Pakistan is actually the traditional law though the said law is not acknowledged by the State. This caused the main problem of the rule of law in the difference between the state laws and the cultural values. These values, customs and so-called traditional laws are the main obstacle to enforce the State law in true letter and spirit which has caused dissatisfaction of the masses and distrust upon the judicial system of the country.

Keywords: consequences, implement, law, Pakistan

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Authors: Pankaj Prashar, Bimlesh Kumar, Ankita Sood, Anamika Gautam

Abstract:

Pharmacovigilance (PV) is a rapidly growing discipline in pharmaceutical industries as an integral part of clinical research and drug development over the past few decades. PV carries a breadth of scope from drug manufacturing to its regulation with safer utilization. The fundamental steps of PV not only includes data collection and verification, coding of drugs with adverse drug reactions, causality assessment and timely reporting to the authorities but also monitoring drug manufacturing, safety issues, product quality and conduction of due diligence. Standardization of adverse event information, collaboration of multiple departments in different companies, preparation of documents in accordance to both governmental as well as non-governmental organizations (FDA, EMA, GVP, ICH) are the advancements in discipline of PV. De-harmonization, lack of predictive drug safety models, improper funding by government, non-reporting, and non-acceptability of ADRs by developing countries and reports directly from patients to the monitoring centres respectively are the major road backs of PV. Mandatory pharmacovigilance reporting, frequent inspections, funding by government, educating and training medical students, pharmacists and nurses in this segment can bring about empowerment in PV. This area needs to be addressed with a sense of urgency for the safe utilization of pharmaceuticals.

Keywords: pharmacovigilance, regulatory, adverse event, drug safety

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