Search results for: economic activity
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 12725

Search results for: economic activity

9995 Investigating the Antibacterial Properties and Omega-3 Levels of Evening Primrose Plant Against Multi-Drug Resistant Bacteria

Authors: A. H. Taghdisi, M. Mirmohammadi, S. Kamali

Abstract:

Evening primrose (Oenothera biennis L.) is a biennial and herbaceous and one of the most important species of medicinal plants in the world. due to the production of unsaturated fatty acids such as linoleic acid, alpha-linolenic acid, etc. in its seeds and roots, and compounds such as kaempferol in its leaves, Evening primrose has important medicinal efficiency such as reducing premenstrual problems, acceleration of wound healing, inhibiting platelet aggregation, sedation of cardiovascular diseases, and treatment of viral infections. The sap of the plant is used to treat warts, and the plant itself is used as a charm against mental and spiritual diseases and poisonous animals. Its leaves have significant antibacterial activity against yellow staphylococci. It is also used in the treatment of poisoning, especially the toxication caused by the consumption of alcoholic beverages, in the treatment of arteriosclerosis and diseases caused by liver cell insufficiency. Low germination and production speed are the problems of evening primrose growth and propagation. In the present study, extracts were obtained from four components (flowers, stems, seeds, leaves) of the evening primrose plant using the Soxhlet apparatus. To measure the antibacterial properties against MDR bacteria, microbial methods, including dilution, cultivation on a plate containing nutrient agar culture medium, and disc diffusion in agar, were performed using Staphylococcus aureus and Escherichia coli bacteria on all four extracts. The maximum antibacterial activity related to the dilution method was obtained in all extracts. In the plate culture method, antibacterial activity was obtained for all extracts in the nutrient agar medium. The maximum diameter of the non-growth halo was obtained in the disc diffusion method in agar in the leaf extract. The statistical analysis of the microbial part was done by one-way ANOVA test (SPSS). By comparing the amount of omega-3 in extracts of Iranian and foreign oils available in the market and the extracts extracted from evening primrose plant samples with gas chromatography, it is shown that the stem extract had the most omega-3 (oleic acid) and compared to the extract of the mentioned oils, it had the highest amount of omega-3 overall. Also, the amount of omega-3 in the extract of Iranian oils was much higher than in the extract of foreign oils. It should be noted that the extract of foreign oils had a more complete composition of omega-3 than the extract of Iranian oils.

Keywords: antibacterial activity, MDR bacteria, evening primrose, omega-3

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9994 Gender-Based Violence in Pakistan: Addressing the Root Causes

Authors: Hafiz Awais Ahmad

Abstract:

This paper aims to examine the root causes of gender-based violence (GBV) in Pakistan and proposes strategies to address this issue. Using a qualitative approach, this study analyzed data from various sources, including interviews with survivors of GBV and experts in the field. The findings revealed that GBV in Pakistan is deeply rooted in patriarchal attitudes and practices, economic insecurity, lack of education, and limited access to justice. The study recommends a multi-faceted approach to address GBV, including legislative reforms, awareness-raising campaigns, economic empowerment, and improved access to justice for survivors. Furthermore, the study highlights the importance of engaging men and boys in efforts to address GBV and promote gender equality. The findings of this study have important implications for policy-makers, practitioners, and researchers working towards ending GBV in Pakistan.

Keywords: gender-based violence, Pakistan, legislative reforms, advocacy

Procedia PDF Downloads 144
9993 Therapeutic Potential of GSTM2-2 C-Terminal Domain and Its Mutants, F157A and Y160A on the Treatment of Cardiac Arrhythmias: Effect on Ca2+ Transients in Neonatal Ventricular Cardiomyocytes

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

Abstract:

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

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

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9992 Nickel Catalyst Promoted with Lanthanum- Alumina for Dry Reforming of Methane

Authors: Radia Imane Fertout

Abstract:

In recent years, the reaction of dry reforming of methane (DRM) has attracted much attention due to its environmental and industrial importance. Various catalysts, including Ni-based catalysts, have been investigated for the DRM. Doping Ni/Al₂O₃ by lanthanum and alkaline earth element may strongly influence solid-state reaction and increases the stability of catalysts due to the lower density and high basicity of these oxides. The effect of SrO on the activity and stability of Ni/Al₂O₃-La₂O₃ in dry reforming of methane was investigated. These catalysts have been prepared with the impregnation method, calcined in air at 450 and 650°C, then characterized by BET surface area, X-ray diffraction (XRD), and scanning electron microscopy (SEM) techniques and tested in DRM. The results showed that the addition of strontium to Ni/Al2O₃-La₂O₃ decreased the specific surface area. XRD results revealed the presence of different phases of Al₂O₃, La(OH)₃, La₂O₂CO₃, and SrCO₃. The catalytic evaluation results showed that adding SrO increased the catalytic activity and stability, that explained by the strong basicity of strontium. SEM analysis after the reaction indicates the formation of carbon over the spent catalyst and that the addition of strontium stabilized the surface of the catalyst.

Keywords: dry reforming of methane, Ni/Al₂O₃-La₂O₃ catalyst, strontium, nickel

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9991 Circular Economy and Remedial Frameworks in Contract Law

Authors: Reza Beheshti

Abstract:

This paper examines remedies for defective manufactured goods in commercial circular economic transactions. The linear ‘take-make-dispose’ model fits well with the conventional remedial framework in which damages are considered the primary remedy. Damages under English Sales Law encourages buyers to look for a substitute seller with broadly similar goods to the ones agreed on in the original contract, enter into contract with this new seller and hence terminate the original contract. By doing so, the buyer ends the contractual relationship. This seems contrary to the core principles of the circular economy: keeping products, components, and materials in longer use, which can partly be achieved by product refurbishment. This process involves returning a product to good working condition by replacing or repairing major components that are faulty or close to failure and making ‘cosmetic’ changes to update the appearance of a product. This remedy has not been widely accepted or applied in commercial cases, which in turn flags up the secondary nature of performance-related remedies. This paper critically analyses the laws concerning the seller’s duty to cure in English law and the extent to which they correspond with core principles of the circular economy. In addition, this paper takes into account the potential of circular economic transactions being characterised as something other than sales. In such situations, the likely outcome will be a license to use products, which may limit the choice of remedy further. Consequently, this paper suggests an outline remedial framework specifically for commercial circular economic transactions in manufactured goods.

Keywords: circular economy, contract law, remedies, English Sales Law

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9990 NiSe-Ni₃Se₂/Multiwalled Carbon Nanotubes as Efficient Electrocatalysts for the Oxygen Evolution Reaction in Alkaline Media

Authors: Oluwaseun A. Oyetade, Roelof J. Kriek

Abstract:

The development of effective catalysts for the oxygen evolution reaction (OER) is of great importance to combat energy-related concerns in the environment. Herein, we report a one-step solvothermal method employed for the fabrication of nickel selenide hybrids (NiSe-Ni₃Se₂) and a series of nickel selenide hybrid/multiwalled carbon nanotube composites (NiSe-Ni₃Se₂/MWCNT) as electrocatalysts for OER in alkaline media. The catalytic activities of these catalysts were investigated via several electrochemical characterization techniques, such as linear sweep voltammetry, chronoamperometric studies at constant potential, electrochemical surface area determination, and Tafel slope calculation, under alkaline conditions. Morphological observations demonstrated the agglomeration of non-uniform NiSe-Ni₃Se₂ microspheres around carbon nanotubes (CNTs), demonstrating the successful synthesis of NiSe-Ni₃Se₂/MWCNT nanocomposites. Among the tested electrocatalysts, the 20% NiSe-Ni₃Se₂/MWCNT nanocomposite demonstrated the highest activity, exhibiting an overpotential of 325 mV to achieve a current density of 10 mA.cm⁻² in 0.1 mol.dm⁻³ KOH solution. The NiSe-Ni₃Se₂/MWCNT nanocomposites showed improved activity toward OER compared to bare NiSe-Ni₃Se₂ hybrids and MWCNTs, exhibiting an overpotential of 528, 392 and 434 mV for 10%, 30% and 50% NiSe-Ni₃Se₂/MWCNT nanocomposites, respectively. These results compare favourably to the overpotential of noble catalysts, such as RuO₂ and IrO₂. Our results imply that the addition of MWCNTs increased the activity of NiSe-Ni₃Se₂ hybrids due to an increased number of catalytic sites, dispersion of NiSe-Ni₃Se₂ hybrid nanoparticles, and electronic conductivity of the nanocomposites. These nanocomposites also demonstrated better long-term stability compared to NiSe-Ni₃Se₂ hybrids and MWCNTs. Hence, NiSe-Ni₃Se₂/MWCNT nanocomposites possess the potential as effective electrocatalysts for OER in alkaline media.

Keywords: carbon nanotubes, electrocatalysts, nanocomposites, nickel selenide hybrids, oxygen evolution reaction

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9989 Evaluation of Anti-inflammatory Activities of Extracts Obtained from Capparis Erythrocarpos In-Vivo

Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

Abstract:

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

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

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9988 An Exposition of Principles of Islamic Fiscal Policy

Authors: Muhammad A. Ishaq, S. U. R. Aliyu

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This paper on an exposition of Islamic fiscal policy attempts to discuss the basic principles of Islamic fiscal policy in an Islamic economy. The paper presents a number of definitions of the subject matter, its nature and its tools of application. Government spending, taxation and public borrowings were identified as the tools of the policy. The paper identifies zakat both as a veritable source of revenue and a major instrument of economic stabilization. Furthermore, the paper presents an algebraic 2-sector and 3-sector models from the basic Keynesian model. The paper posits that in view of uniqueness of its instruments, absence of interest rate in the economy and the policy’s derive towards socioeconomic justice and redistribution, Islamic fiscal policy is capable of stabilizing Islamic economy and ushering it into the path of long term economic growth and prosperity.

Keywords: automatic built-in-stabilizers, government spending, Islamic fiscal policy, taxation, zakat

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9987 Synthesis and Pharmaco-Potential Evaluation of Quinoline Hybrids

Authors: Paul Awolade, Parvesh Singh

Abstract:

The global threat of pathogenic resistance to available therapeutic agents has become a menace to clinical practice, public health and man’s existence inconsequential. This has therefore led to an exigency in the development of new molecular scaffolds with profound activity profiles. In this vein, a versatile synthetic tool for accessing new molecules by incorporating two or more pharmacophores into a single entity with the unique ability to be recognized by multiple receptors hence leading to an improved bioactivity, known as molecular hybridization, has been explored with tremendous success. Accordingly, aware of the similarity in pharmacological activity spectrum of quinoline and 1,2,3-triazole pharmacophores such as; anti-Alzheimer, anticancer, anti-HIV, antimalarial and antimicrobial to mention but a few, the present study sets out to synthesize hybrids of quinoline and 1,2,3-triazole. The hybrids were accessed via click chemistry using copper catalysed azide-alkyne 1,3-dipolar cycloaddition reaction. All synthesized compounds were evaluated for their pharmaco-potential in an antimicrobial assay out of which the 3-OH derivative emerged as the most active with MIC value of 4 μg/mL against Cryptococcus neoformans; a value superior to standard Fluconazole and comparable to Amphotericin B. Structures of synthesized hybrids were elucidated using appropriate spectroscopic techniques (1H, 13C and 2D NMR, FT-IR and HRMS).

Keywords: bioisostere, click chemistry, molecular hybridization, quinoline, 1, 2, 3-triazole

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9986 Determinants of the Shadow Economy with an Islamic Orientation: An Application to Organization of Islamic Cooperation and Non-Organization of Islamic Cooperation Countries

Authors: Shabeer Khan

Abstract:

The main objective of Islamic Finance is to promote social justice thorough financial inclusion and redistribution of economic resources between rich and poor. The approach of Islamic finance is more comprehensive in nature and covers both formal and informal sectors of the economy, first, through reducing the gap between both sectors, and second by using specific Islamic values to reallocate the wealth between formal and informal sectors. Applying Generalized Method of Movements (GMM) to the annual data spanning from 1995-2015 for 141 countries, this study explores the determinants of informal business sector in Organization of Islamic Cooperation (OIC) countries and then compares with Non-OIC countries. Economic freedom and institutions variables as well as economic growth and money supply are found to reduce informal business sector in both OIC and Non-OIC nations while government expenditure are found to increase informal business sector in both group of nations. Informal Business sector remain the same in both types of countries but still the majority Muslim population in OIC economies create main difference between both groups of nations and justify the potential role of Islamic Finance in informal business sector in OIC nations. The study suggests that institutions quality should be improved and entrepreneurs’ friendly business environment must be provided. This study refines the main features of informal business sector and discuss their implications on policy designing and implementation, particularly in the context of Islamic finance fight against poverty, inequality and improving living standards of informal sector participants in OIC countries.

Keywords: Islamic finance, informal Business Sector, Generalized Method of Movements (GMM) and OIC

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9985 Interdisciplinary Approach for Economic Production of Oil and Gas Reserves: Application of Geothermal Energy for Enhanced Oil Recovery

Authors: Dharmit Viroja, Prerakkumar Shah, Rajanikant Gajera, Ruchit Shah

Abstract:

With present scenario of aging oil and gas fields with high water cuts, volatile oil prices and increasing greenhouse gas emission, the need for alleviating such issues has necessitated for oil and gas industry to make the maximum out of available assets, infrastructure and reserves in mother Earth. Study undertaken emphasizes on utilizing Geothermal Energy under specific reservoir conditions for Enhanced oil Recovery (EOR) to boost up production. Allied benefits of this process include mitigation of electricity problem in remote fields and controlled CO-emission. Utilization of this energy for EOR and increasing economic life of field could surely be rewarding. A new way to value oil lands would be considered if geothermal co-production is integrated in the field development program. Temperature profile of co-produced fluid across its journey is a pivotal issue which has been studied. Geo pressured reservoirs resulting from trapped brine under an impermeable bed is also a frontier for exploitation. Hot geothermal fluid is a by-product of large number of oil and gas wells, historically this hot water has been seen as an inconvenience; however, it can be looked at as a useful resource. The production of hot fluids from abandoned and co-production of hot fluids from producing wells has potential to prolong life of oil and gas fields. The study encompasses various factors which are required for use of this technology and application of this process across various phases of oil and gas value chain. Interdisciplinary approach in oil and gas value chain has shown potential for economic production of estimated oil and gas reserves.

Keywords: enhanced oil recovery, geo-pressured reservoirs, geothermal energy, oil and gas value chain

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9984 In Vitro Antibacterial Activity of Some Medicinal Plants Against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus

Authors: Tesleem Adewale Ibrahim

Abstract:

Introduction: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has been slowly rising in Nigeria for the past few decades. Therefore, novel classes of antibiotics are indispensable to combat the increased incidence of newly emerging multidrug-resistant bacteria like MRSA. Plants have been commonly used in popular medicine of most cultures for the treatment of disease. The in vitro antibacterial activity of some Nigerian common medicinal plants used in traditional medicine has been reported. The aim of this study was to investigate the antibacterial and anti-biofilm of these native plants (Entada abysinnica (leaves), Croton macrostachyus (leaves), Bridelia speciosa (seeds, bark), and Aframomum melegueta (leaves, seeds, and stem) collected in Southwestern Nigeria against a panel of seven biofilm-forming MRSA. Methods: Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of the plant extracts against MRSA were determined by the broth dilution method, and the anti-biofilm assay of the most potent plant extract was performed. Result: The results revealed that, of the four plants, water extracts of leaves of Entada abysinnica, leaves of Croton macrostachyus, seeds and bark Bridelia speciosa, and seeds of Aframomum melegueta exhibited significant antibacterial activity. Based on the MIC/MBC ratio, the extracts of these plants were determined to be bacteriostatic in nature. Anti-biofilm assay showed that the extract of seeds of Aframomum melegueta and leaves of Croton macrostachyus fairly inhibited the growth of MRSA in the preformed biofilm matrix. Conclusion: These four medicinal plant species may represent a source of alternative drugs derived from plant extracts based on folklore use and ethnobotanical knowledge from southwest Nigeria.

Keywords: extract, MRSA, antibacterial, biofilm, medicinal plants

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9983 Strategies for Medium Sized Construction Firms to Survive the Current Economic Conditions That Is Compounded by the Most Recent COVID-19 Pandemic in Nigeria

Authors: Aloysius Colman Chukwuemeka Ezeabasili, Chibuike Patrick Ezeabasili

Abstract:

Medium Sized Construction Companies in Nigeria are those employing 50-250 workers that are mostly involved in roads, Commercial and domestic building Construction, among others. These companies are in the majority and contribute immensely to infrastructural development in Nigeria. Despite the last eight years of economic downturn and the past years of COVID-19 pandemic, signs of these Companies recovering from the economic recession and pandemic seem bright. Nigeria has recorded 213,000 confirmed cases 3968 deaths from COVID-19 as at now. These medium sized companies are currently trying to explore various opportunities to grow their businesses to achieve competitive advantages over others by studying and improving on their bidding efficiency, Strategies for selecting businesses, bidding markup Strategies, and cash flow. These strategies were studied through the recruitment of construction experts and professionals. Many of them have acquired new technologies that have impacted positively on their strategies. The impact of these technologies like the BIM, e-tendering, conditions of contract, and claim management strategies are advantages to them and has given them good advantages over their peers. Monte Carlo solution, Swot analysis, and average bid methods have also clearly added advantages to bidding practices. New and existing strategies are Scrutinized, and training of young Nigerians in advanced countries to acquire knowledge in best practices have elevated some of these companies. The Covid-19 has not been very harsh to Nigeria, and the country is surely not as devastated as the advanced countries. Nigeria has therefore been able to cope with the combination of the downturn and the pandemic.

Keywords: medium sized construction companies, competitive advantage, new bidding technologies, Nigeria

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9982 The Chinese Inland-Coastal Inequality: The Role of Human Capital and the Crisis Watershed

Authors: Iacopo Odoardi, Emanuele Felice, Dario D'Ingiullo

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We investigate the role of human capital in the Chinese inland-coastal inequality and how the consequences of the 2007-2008 crisis may induce China to refocus its development path on human capital. We compare panel data analyses for two periods for the richer/coastal and the relatively poor/inland provinces. Considering the rapid evolution of the Chinese economy and the changes forced by the international crisis, we wonder if these events can lead to rethinking local development paths, fostering greater attention on the diffusion of higher education. We expect that the consequences on human capital may, in turn, have consequences on the inland/coastal dualism. The focus on human capital is due to the fact that the growing differences between inland and coastal areas can be explained by the different local endowments. In this respect, human capital may play a major role and should be thoroughly investigated. To assess the extent to which human capital has an effect on economic growth, we consider a fixed-effects model where differences among the provinces are considered parametric shifts in the regression equation. Data refer to the 31 Chinese provinces for the periods 1998-2008 and 2009-2017. Our dependent variable is the annual variation of the provincial gross domestic product (GDP) at the prices of the previous year. Among our regressors, we include two proxies of advanced human capital and other known factors affecting economic development. We are aware of the problem of conceptual endogeneity of variables related to human capital with respect to GDP; we adopt an instrumental variable approach (two-stage least squares) to avoid inconsistent estimates. Our results suggest that the economic strengths that influenced the Chinese take-off and the dualism are confirmed in the first period. These results gain relevance in comparison with the second period. An evolution in local economic endowments is taking place: first, although human capital can have a positive effect on all provinces after the crisis, not all types of advanced education have a direct economic effect; second, the development path of the inland area is changing, with an evolution towards more productive sectors which can favor higher returns to human capital. New strengths (e.g., advanced education, transport infrastructures) could be useful to foster development paths of inland-coastal desirable convergence, especially by favoring the poorer provinces. Our findings suggest that in all provinces, human capital can be useful to promote convergence in growth paths, even if investments in tertiary education seem to have a negative role, most likely due to the inability to exploit the skills of highly educated workers. Furthermore, we observe important changes in the economic characteristics of the less developed internal provinces. These findings suggest an evolution towards more productive economic sectors, a greater ability to exploit both investments in fixed capital and the available infrastructures. All these aspects, if connected with the improvement in the returns to human capital (at least at the secondary level), lead us to assume a better reaction (i.e., resilience) of the less developed provinces to the crisis effects.

Keywords: human capital, inland-coastal inequality, Great Recession, China

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9981 How to Evaluate the Contribution of Social Finance to Regional Economy

Authors: Jungeun Cho

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Social finance has received increasing attention as a means to promote the growth of regional economies. Despite the plenty of research discussed their critical role and functions in regional economic development such as the financing and promotion of co-operatives or social enterprises and the offering credit to the financially excluded in the region, however, rarely are efforts made to measure the contribution of social finance in the regional economy. It is essential to establish an evaluation model in order to encourage social finance institutions to perform their supposed role and functions on regional economic development. The objective of this paper is to formulate an evaluation model of the contribution of social finance to the regional economy through an analytic hierarchy process (AHP) approach. This study is expected to provide useful guidelines for social finance institutions’ strategies and the policies of local or central government regarding social finance.

Keywords: social finance, regional economy, social economy, policies of local or central government

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9980 CO₂ Conversion by Low-Temperature Fischer-Tropsch

Authors: Pauline Bredy, Yves Schuurman, David Farrusseng

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To fulfill climate objectives, the production of synthetic e-fuels using CO₂ as a raw material appears as part of the solution. In particular, Power-to-Liquid (PtL) concept combines CO₂ with hydrogen supplied from water electrolysis, powered by renewable sources, which is currently gaining interest as it allows the production of sustainable fossil-free liquid fuels. The proposed process discussed here is an upgrading of the well-known Fischer-Tropsch synthesis. The concept deals with two cascade reactions in one pot, with first the conversion of CO₂ into CO via the reverse water gas shift (RWGS) reaction, which is then followed by the Fischer-Tropsch Synthesis (FTS). Instead of using a Fe-based catalyst, which can carry out both reactions, we have chosen the strategy to decouple the two functions (RWGS and FT) on two different catalysts within the same reactor. The FTS shall shift the equilibrium of the RWGS reaction (which alone would be limited to 15-20% of conversion at 250°C) by converting the CO into hydrocarbons. This strategy shall enable optimization of the catalyst pair and thus lower the temperature of the reaction thanks to the equilibrium shift to gain selectivity in the liquid fraction. The challenge lies in maximizing the activity of the RWGS catalyst but also in the ability of the FT catalyst to be highly selective. Methane production is the main concern as the energetic barrier of CH₄ formation is generally lower than that of the RWGS reaction, so the goal will be to minimize methane selectivity. Here we report the study of different combinations of copper-based RWGS catalysts with different cobalt-based FTS catalysts. We investigated their behaviors under mild process conditions by the use of high-throughput experimentation. Our results show that at 250°C and 20 bars, Cobalt catalysts mainly act as methanation catalysts. Indeed, CH₄ selectivity never drops under 80% despite the addition of various protomers (Nb, K, Pt, Cu) on the catalyst and its coupling with active RWGS catalysts. However, we show that the activity of the RWGS catalyst has an impact and can lead to longer hydrocarbons chains selectivities (C₂⁺) of about 10%. We studied the influence of the reduction temperature on the activity and selectivity of the tandem catalyst system. Similar selectivity and conversion were obtained at reduction temperatures between 250-400°C. This leads to the question of the active phase of the cobalt catalysts, which is currently investigated by magnetic measurements and DRIFTS. Thus, in coupling it with a more selective FT catalyst, better results are expected. This was achieved using a cobalt/iron FTS catalyst. The CH₄ selectivity dropped to 62% at 265°C, 20 bars, and a GHSV of 2500ml/h/gcat. We propose that the conditions used for the cobalt catalysts could have generated this methanation because these catalysts are known to have their best performance around 210°C in classical FTS, whereas the iron catalysts are more flexible but are also known to have an RWGS activity.

Keywords: cobalt-copper catalytic systems, CO₂-hydrogenation, Fischer-Tropsch synthesis, hydrocarbons, low-temperature process

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9979 The Roots of the Robust and Looting Economy (poverty and inequality) in Iran after the 1979 Revolution, From the Perspective of Acem Oglu & Robinson theory

Authors: Vorya Shabrandi

Abstract:

The study factors of poverty and inequality causes in countries is the subject of many scholars and economists in the last century, theorists in various areas of economic science know different factors as the roots of poverty and inequality in Iran after the 1979 revolution. Economists have emphasized political elements and political scientists on political elements. This research reviews the political economy of poverty and corruption in Iran after the revolution. The findings of this research, based on AcemOgluand Robinson theory, show how the institutional structural dependence of Iran's economy to raw has led to the growth of its non-economic economic institutions and its consequence of the continuity of the release and looting economy and poverty and inequality in Iran's political economy Is. This research was carried out using descriptive-analytical and comparative methods. Many economists try to justify the conditions of the country based on war, sanctions; And the external factors, and ... knows. In this study, we tried to examine the roots of poverty and the looting economy of Iran by implementing Research AcemOgluand Robinson on the institutions and roots of poverty. Looking for a framework for understanding why countries, such as Iran, the reason for the difference in revenue in different countries, as well as the poor or wealth of countries, regardless of the non-effective and non-professional institutions, and why inefficient institutions in some countries, such as Iran, such as Iran It remains and does not have a voluntary political powers to change these institutions. Findings The research shows that institutions are broadly the main reason for the roots of the robust and looting economy (poverty and inequality) in Iran.

Keywords: Iran, plunderable (Loot) economy, raw shopping, poverty and inequality, acem oglu and robinson, non-inclusive institutions

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9978 Long Short-Term Memory Based Model for Modeling Nicotine Consumption Using an Electronic Cigarette and Internet of Things Devices

Authors: Hamdi Amroun, Yacine Benziani, Mehdi Ammi

Abstract:

In this paper, we want to determine whether the accurate prediction of nicotine concentration can be obtained by using a network of smart objects and an e-cigarette. The approach consists of, first, the recognition of factors influencing smoking cessation such as physical activity recognition and participant’s behaviors (using both smartphone and smartwatch), then the prediction of the configuration of the e-cigarette (in terms of nicotine concentration, power, and resistance of e-cigarette). The study uses a network of commonly connected objects; a smartwatch, a smartphone, and an e-cigarette transported by the participants during an uncontrolled experiment. The data obtained from sensors carried in the three devices were trained by a Long short-term memory algorithm (LSTM). Results show that our LSTM-based model allows predicting the configuration of the e-cigarette in terms of nicotine concentration, power, and resistance with a root mean square error percentage of 12.9%, 9.15%, and 11.84%, respectively. This study can help to better control consumption of nicotine and offer an intelligent configuration of the e-cigarette to users.

Keywords: Iot, activity recognition, automatic classification, unconstrained environment

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9977 Probiotic Potential and Antimicrobial Activity of Enterococcus faecium Isolated from Chicken Caecal and Fecal Samples

Authors: Salma H. Abu Hafsa, A. Mendonca, B. Brehm-Stecher, A. A. Hassan, S. A. Ibrahim

Abstract:

Enterococci are important inhabitants of the animal intestine and are widely used in probiotic products. A probiotic strain is expected to possess several desirable properties in order to exert beneficial effects. Therefore, the objective of this study was to isolate and characterize strains of Enterococcus sp. from chicken cecal and fecal samples to determine potential probiotic properties. Enterococci were isolated from thirty one chicken cecal and fecal samples collected from a local farm. In vitro studies were performed to assess antibacterial activity (using agar well diffusion and cell free supernatant broth technique against Salmonella enterica serotype Enteritidis), susceptibility to antibiotics (amoxycillin, cotrimoxazole, chloramphenicol, cefuroxime, ceftriaxone, ciprofloxacin, and nalidixic acid), survival in acidic conditions, resistance to bile salts, and their survival during simulated gastric juice conditions at pH 2.5. Isolates were identified using biochemical and molecular assays (API 50 CHL, and API ZYM kits followed by 16S rDNA gene sequence analysis). Two strains were identified, of which, Enteroccocus faecium was capable of inhibiting the growth of S. enteritidis and was susceptible to a wide range of antibiotics. In addition, the isolated strain exhibited significant resistance under highly acidic conditions (pH=2.5) for 8 hours and survived well in bile salt at 0.2% for 24 hours and showing ability to survive in the presence of simulated gastric juice at pH 2.5. Based on these results, the E. faecium isolate fulfills some of the criteria to be considered as a probiotic strain and therefore, could be used as a feed additive with good potential for controlling S. enteritidis in chickens. However, in vivo studies are needed to determine the safety of the strain.

Keywords: acid tolerance, antimicrobial activity, Enterococcus faecium, probiotic

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9976 Ergonomics Management and Sustainability: An Exploratory Study Applied to Automaker Industry in South of Brazil

Authors: Giles Balbinotti, Lucas Balbinotti, Paula Hembecker

Abstract:

The management of the productive process project activities, for the conception of future work and for the financial health of the companies, is an important condition in an organizational model that corroborates the management of the human aspects and their variabilities existing in the work. It is important to seek, at all levels of the organization, understanding and consequent cultural change, and so that factors associated with human aspects are considered and prioritized in the projects. In this scenario, the central question of research for this study is placed from the context of the work, in which the managers and project coordinators are inserted, as follows: How is the top management convinced, in the design stages, to take The ‘Ergonomics’ as strategy for the performance and sustainability of the business? In this perspective, this research has as general objective to analyze how the application of the management of the human aspects in a real project of productive process in the automotive industry, including the activity of the manager and coordinator of the project beyond the strategies of convincing to act in the ergonomics of design. For this, the socio-technical and ergonomic approach is adopted, given its anthropocentric premise in the sense of acting on the social system simultaneously to the technical system, besides the support of the Modapts system that measures the non-value-added times and the correlation with the Critical positions. The methodological approach adopted in this study is based on a review of the literature and the analysis of the activity of the project coordinators of an industry, including the management of human aspects in the context of work variability and the strategies applied in project activities. It was observed in the study that the loss of performance of the serial production lines reaches the important number of the order of 30%, which can make the operation with not value-added, and this loss has as one of the causes, the ergonomic problems present in the professional activity.

Keywords: human aspects in production process project, ergonomics in design, sociotechnical project management, sociotechnical, ergonomic principles, sustainability

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9975 Modelling Residential Space Heating Energy for Romania

Authors: Ion Smeureanu, Adriana Reveiu, Marian Dardala, Titus Felix Furtuna, Roman Kanala

Abstract:

This paper proposes a linear model for optimizing domestic energy consumption, in Romania. Both techno-economic and consumer behavior approaches have been considered, in order to develop the model. The proposed model aims to reduce the energy consumption, in households, by assembling in a unitary model, aspects concerning: residential lighting, space heating, hot water, and combined space heating – hot water, space cooling, and passenger transport. This paper focuses on space heating domestic energy consumption model, and quantify not only technical-economic issues, but also consumer behavior impact, related to people decision to envelope and insulate buildings, in order to minimize energy consumption.

Keywords: consumer behavior, open source energy modeling system (OSeMOSYS), MARKAL/TIMES Romanian energy model, virtual technologies

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9974 Identifying Principle Components Affecting Competitiveness of Thai Automotive Parts Industry

Authors: Thanatip Lerttanaporn, Tuanjai Somboonwiwat, Charoenchai Khompatraporn

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The automotive parts industry is one of the vital sectors in Thai economy and now is facing a greater competition from ASEAN Economic Community (AEC). This article identifies important factors that impact the competitiveness of Thai automotive parts industry. There are eight groups of factors with a total of 58 factors. Due to a variety of factors, the Exploratory Factor Analysis and Principle Component Analysis have been applied to classify factors into groups or principle components. The results show that there are 15 groups and four of them are critical, covering 80% of important value. These four critical groups are then used to formulate strategies to improve the competitiveness of the Thai automotive parts industry.

Keywords: factor analysis, Thai automotive parts, principle components, exploratory factor, ASEAN economic community

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9973 Psychological Distress and Quality of Life in Inflammatory Bowel Disease Patients: The Role of Dispositional Mindfulness

Authors: Kelly E. Tow, Peter Caputi, Claudia Rogge, Thomas Lee, Simon R. Knowles

Abstract:

Inflammatory Bowel Disease (IBD) is a serious chronic health condition, characterised by inflammation of the gastrointestinal tract. Individuals with active IBD experience severe abdominal symptoms, which can adversely impact their physical and mental health, as well as their quality of life (QoL). Given that stress may exacerbate IBD symptoms and is frequently highlighted as a contributing factor for the development of psychological difficulties and poorer QoL, it is vital to investigate stress-management strategies aimed at improving the lives of those with IBD. The present study extends on the limited research in IBD cohorts by exploring the role of dispositional mindfulness and its impact on psychological well-being and QoL. The study examined how disease activity and dispositional mindfulness were related to psychological distress and QoL in a cohort of IBD patients. The potential role of dispositional mindfulness as a moderator between stress and anxiety, depression and QoL in these individuals was also examined. Participants included 47 patients with a clinical diagnosis of IBD. Each patient completed a series of psychological questionnaires and was assessed by a gastroenterologist to determine their disease activity levels. Correlation analyses indicated that disease activity was not significantly related to psychological distress or QoL in the sample of IBD patients. However, dispositional mindfulness was inversely related to psychological distress and positively related to QoL. Furthermore, moderation analyses demonstrated a significant interaction between stress and dispositional mindfulness on anxiety. These findings demonstrate that increased levels of dispositional mindfulness may be beneficial for individuals with IBD. Specifically, the results indicate positive links between dispositional mindfulness, general psychological well-being and QoL, and suggest that dispositional mindfulness may attenuate the negative impacts of stress on levels of anxiety in IBD patients. While further research is required to validate and expand on these findings, the current study highlights the importance of addressing psychological factors in IBD and indicates support for the use of mindfulness-based interventions for patients with the disease.

Keywords: anxiety, depression, dispositional mindfulness, inflammatory bowel disease, quality of life, stress

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9972 Beijerinckia indica Extracellular Extract Mediated Green Synthesis of Silver Nanoparticles with Antioxidant and Antibacterial Activities against Clinical Pathogens

Authors: Gopalu Karunakaran, Matheswaran Jagathambal, Nguyen Van Minh, Evgeny Kolesnikov, Denis Kuznetsov

Abstract:

This work investigated the use of Beijerinckia indica extracellular extract for the synthesis of silver nanoparticles using AgNO3. The formation of nanoparticles was confirmed by different methods, such as UV-Vis absorption spectroscopy, XRD, FTIR, EDX, and TEM analysis. The formation of silver nanoparticles (AgNPs) was confirmed by the change in color from light yellow to dark brown. The absorbance peak obtained at 430 nm confirmed the presence of silver nanoparticles. The XRD analysis showed the cubic crystalline phase of the synthesized nanoparticles. FTIR revealed the presence of groups that acts as stabilizing and reducing agents for silver nanoparticles formation. The synthesized silver nanoparticles were generally found to be spherical in shape with size ranging from 5 to 20 nm, as evident by TEM analysis. These nanoparticles were found to inhibit pathogenic bacterial strains. This work proved that the bacterial extract is a potential eco-friendly candidate for the synthesis of silver nanoparticles with promising antibacterial and antioxidant properties. 

Keywords: antioxidant activity, antimicrobial activity, Beijerinckia indica, characterisation, extracellular extracts, silver nanoparticles

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9971 Data-Driven Dynamic Overbooking Model for Tour Operators

Authors: Kannapha Amaruchkul

Abstract:

We formulate a dynamic overbooking model for a tour operator, in which most reservations contain at least two people. The cancellation rate and the timing of the cancellation may depend on the group size. We propose two overbooking policies, namely economic- and service-based. In an economic-based policy, we want to minimize the expected oversold and underused cost, whereas, in a service-based policy, we ensure that the probability of an oversold situation does not exceed the pre-specified threshold. To illustrate the applicability of our approach, we use tour package data in 2016-2018 from a tour operator in Thailand to build a data-driven robust optimization model, and we tested the proposed overbooking policy in 2019. We also compare the data-driven approach to the conventional approach of fitting data into a probability distribution.

Keywords: applied stochastic model, data-driven robust optimization, overbooking, revenue management, tour operator

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9970 The Potential Roles of Digital Technologies in Developing Children's Artistic Ability and Promoting Creative Activity in Children Aged

Authors: Aber Aboalgasm, Rupert Ward, Ruth Taylor, Jonathan Glazzard

Abstract:

Teaching art by digital means is a big challenge for the majority of teachers of art and artistic design courses in primary education schools. These courses can clearly identify relationships between art, technology, and creativity in the classroom .The aim of this article is to present a modern way of teaching art, using digital tools in the art classroom in order to improve creative ability in pupils aged between 9 and 11 years; it also presents a conceptual model for creativity based on digital art. The model could be useful for pupils interested in learning drawing and using an e-drawing package, and for teachers who are interested in teaching their students modern digital art, and improving children’s creativity. This model is designed to show the strategy of teaching art through technology, in order for children to learn how to be creative. This will also help education providers to make suitable choices about which technological approaches they should choose to teach students and enhance their creative ability. It is also expected that use of this model will help to develop social interactive qualities that may improve intellectual ability.

Keywords: digital tools, motivation, creative activity, education

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9969 Techno-Economic Analysis (TEA) of Circular Economy Approach in the Valorisation of Pig Meat Processing Wastes

Authors: Ribeiro A., Vilarinho C., Luisa A., Carvalho J

Abstract:

The pig meat industry generates large volumes of by- and co-products like blood, bones, skin, trimmings, organs, viscera, and skulls, among others, during slaughtering and meat processing and must be treated and disposed of ecologically. The yield of these by-products has been reported to account for about 10% to 15% of the value of the live animal in developed countries, although animal by-products account for about two-thirds of the animal after slaughter. It was selected for further valorization of the principal wastes produced throughout the value chain of pig meat production: Pig Manure, Pig Bones, Fats, Skins, Pig Hair, Wastewater, Wastewater sludges, and other animal subproducts type III. According to the potential valorization options, these wastes will be converted into Biomethane, Fertilizers (phosphorus and digestate), Hydroxyapatite, and protein hydrolysates (Keratin and Collagen). This work includes comprehensive technical and economic analyses (TEA) for each valorization route or applied technology. Metrics such as Net Present Value (NPV), Internal Rate of Return (IRR), and payback periods were used to evaluate economic feasibility. From this analysis, it can be concluded that, for Biogas Production, the scenarios using pig manure, wastewater sludges and mixed grass and leguminous wastes presented a remarkably high economic feasibility. Scenarios showed high economic feasibility with a positive payback period, NPV, and IRR. The optimal scenario combining pig manure with mixed grass and leguminous wastes had a payback period of 1.2 years and produced 427,6269 m³ of biomethane annually. Regarding the Chemical Extraction of Phosphorous and Nitrogen, results proved that the process is economically unviable due to negative cash flows despite high recovery rates. The TEA of Hydrolysis and Extraction of Keratin Hydrolysates indicate that a unit processing and valorizing 10 tons of pig hair per year for the production of keratin hydrolysate has an NPV of 907,940 €, an IRR of 13.07%, and a Payback period of 5.41 years. All of these indicators suggest a highly potential project to explore in the future. On the opposite, the results of Hydrolysis and Extraction of Collagen Hydrolysates showed a process economically unviable with negative cash flows in all scenarios due to the high-fat content in raw materials. In fact, the results from the valorization of 10 tons of pig skin had a negative cash flow of 453 743,88 €. TEA results of Extraction and purification of Hydroxyapatite from Pig Bones with Pyrolysis indicate that unit processing and valorizing 10 tons of pig bones per year for the production of hydroxyapatite has an NPV of 1 274 819,00 €, an IRR of 65.43%, and a Payback period of 1,5 years over a timeline of 10 years with a discount rate of 10%. These valorization routes, circular economy and bio-refinery approach offer significant contributions to sustainable bio-based operations within the agri-food industry. This approach transforms waste into valuable resources, enhancing both environmental and economic outcomes and contributing to a more sustainable and circular bioeconomy.

Keywords: techno-economic analysis (TEA), pig meat processing wastes, circular economy, bio-refinery

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9968 Plasma Spray Deposition of Bio-Active Coating on Titanium Alloy (Ti-6Al-4V) Substrate

Authors: Renu Kumari, Jyotsna Dutta Majumdar

Abstract:

In the present study, composite coating consisting of hydroxyapatite (HA) + 50 wt% TiO2 has been developed on Ti-6Al-4V substrate by plasma spray deposition technique. Followed by plasma spray deposition, detailed surface roughness and microstructural characterization were carried out by using optical profilometer and scanning electron microscopy (SEM), respectively. The composition and phase analysis were carried out by energy-dispersive X-ray spectroscopy analysis, and X-ray diffraction (XRD) technique, respectively. The bio-activity behavior of the uncoated and coated samples was also compared by dipping test in Hank’s solution. The average surface roughness of the coating was 10 µm (as compared to 0.5 µm of as-received Ti-6Al-4V substrate) with the presence of porosities. The microstructure of the coating was found to be continuous with the presence of solidified splats. A detailed XRD analysis shows phase transformation of TiO2 from anatase to rutile, decomposition of hydroxyapatite, and formation of CaTiO3 phase. Standard dipping test confirmed a faster kinetics of deposition of calcium phosphate in the coated HA+50% wt.% TiO2 surface as compared to the as-received substrate.

Keywords: titanium, plasma spraying, microstructure, bio-activity, TiO2, hydroxyapatite

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9967 Rethinking Africa's 'Great Runner': Authoritarianism and Development in Post-Cold War Ethiopia

Authors: Frew Yirgalem Mane

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This study has examined Africa’s experiment with authoritarian model of development drawing from the experience of Ethiopia. With the tectonic crisis of neoliberal ideology, the dominant policy agenda in Africa pertains to bringing the state back to development. More concretely, countries epitomized by Ethiopia, Rwanda and Uganda have been constructing a highly interventionist state with authoritarian character. The central motive appears to facilitate development and salvage people out of appalling and grinding poverty. Each country warrants closer inspection. However, this study focuses on Ethiopia- a country often applauded as ‘Africa’s Great Run’ for delivering socio-economic success over the past two decades. In fact, inspired by East Asia’s including Chinese model of authoritarian development, Ethiopia orchestrated a vanguard party, centralized rent control system with politicized bureaucracy and militaristic mobilization resources for development. This arrangement may explain Ethiopia economic success story as one the fastest growing countries in the world. However, this paper detected, Ethiopia’s attempt to bring the state back in development has precipitated institutionalization of a new breed of authoritarianism and informalization of public institutions. Ethiopia’s model of state-led development may constitute a noticeable shift away from the vengeful adherence to neoliberal policies. However, the manner the model has been practiced proved to be neither smooth nor appears to address Ethiopia’s aspiration for political and economic transformation. Partly, this can be illustrated by recent widespread grievances that fed into the popular uprising and animated opposition against the state. Sources of the grievance are complex, but they are highly ingrained with the way the authoritarian model of development is functioning and also the model’s dis-functioning in terms of benefiting people. In light of these findings, the study has arrived at the following conclusion. Africa’s attempt to emulate development models from other countries is not such a ‘bad’ thing. However, emulation makes sense if it is contextualized and sensitive to complex local socio-economic interests.

Keywords: Africa, authoritarianism, development, Ethiopia, neoliberalism

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9966 Use of Zikani’s Ribosome Modulating Agents for Treating Recessive Dystrophic & Junctional Epidermolysis Bullosa with Nonsense Mutations

Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

Abstract:

Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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