Search results for: epidermal growth factor receptor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 11351

Search results for: epidermal growth factor receptor

11141 Modified Acetamidobenzoxazolone Based Biomarker for Translocator Protein Mapping during Neuroinflammation

Authors: Anjani Kumar Tiwari, Neelam Kumari, Anil Mishra

Abstract:

The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: TSPO, PET, imaging, Acetamidobenzoxazolone

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11140 Economic Analysis of Endogenous Growth Model with ICT Capital

Authors: Shoji Katagiri, Hugang Han

Abstract:

This paper clarifies the role of ICT capital in Economic Growth. Albeit ICT remarkably contributes to economic growth, there are few studies on ICT capital in ICT sector from theoretical point of view. In this paper, production function of ICT which is used as input of intermediate good in final good and ICT sectors is incorporated into our model. In this setting, we analyze the role of ICT on balance growth path and show the possibility of general equilibrium solutions for this model. Through the simulation of the equilibrium solutions, we find that when ICT impacts on economy and economic growth increases, it is necessary that increases of efficiency at ICT sector and of accumulation of non-ICT and ICT capitals occur simultaneously.

Keywords: endogenous economic growth, ICT, intensity, capital accumulation

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11139 On Differential Growth Equation to Stochastic Growth Model Using Hyperbolic Sine Function in Height/Diameter Modeling of Pines

Authors: S. O. Oyamakin, A. U. Chukwu

Abstract:

Richard's growth equation being a generalized logistic growth equation was improved upon by introducing an allometric parameter using the hyperbolic sine function. The integral solution to this was called hyperbolic Richard's growth model having transformed the solution from deterministic to a stochastic growth model. Its ability in model prediction was compared with the classical Richard's growth model an approach which mimicked the natural variability of heights/diameter increment with respect to age and therefore provides a more realistic height/diameter predictions using the coefficient of determination (R2), Mean Absolute Error (MAE) and Mean Square Error (MSE) results. The Kolmogorov-Smirnov test and Shapiro-Wilk test was also used to test the behavior of the error term for possible violations. The mean function of top height/Dbh over age using the two models under study predicted closely the observed values of top height/Dbh in the hyperbolic Richard's nonlinear growth models better than the classical Richard's growth model.

Keywords: height, Dbh, forest, Pinus caribaea, hyperbolic, Richard's, stochastic

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11138 The Effect of Dopamine D2 Receptor TAQ A1 Allele on Sprinter and Endurance Athlete

Authors: Öznur Özge Özcan, Canan Sercan, Hamza Kulaksız, Mesut Karahan, Korkut Ulucan

Abstract:

Genetic structure is very important to understand the brain dopamine system which is related to athletic performance. Hopefully, there will be enough studies about athletics performance in the terms of addiction-related genetic markers in the future. In the present study, we intended to investigate the Receptor-2 Gene (DRD2) rs1800497, which is related to brain dopaminergic system. 10 sprinter and 10 endurance athletes were enrolled in the study. Real-Time Polymerase Chain Reaction method was used for genotyping. According to results, A1A1, A1A2 and A2A2 genotypes in athletes were 0 (%0), 3 (%15) and 17 (%85). A1A1 genotype was not found and A2 allele was counted as the dominating allele in our cohort. These findings show that dopaminergic mechanism effects on sport genetic may be explained by the polygenic and multifactorial view.

Keywords: addiction, athletic performance, genotype, sport genetics

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11137 The 5-HT1A Receptor Biased Agonists, NLX-101 and NLX-204, Elicit Rapid-Acting Antidepressant Activity in Rat Similar to Ketamine and via GABAergic Mechanisms

Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

Abstract:

The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

Procedia PDF Downloads 105
11136 An Alternative Richards’ Growth Model Based on Hyperbolic Sine Function

Authors: Samuel Oluwafemi Oyamakin, Angela Unna Chukwu

Abstract:

Richrads growth equation being a generalized logistic growth equation was improved upon by introducing an allometric parameter using the hyperbolic sine function. The integral solution to this was called hyperbolic Richards growth model having transformed the solution from deterministic to a stochastic growth model. Its ability in model prediction was compared with the classical Richards growth model an approach which mimicked the natural variability of heights/diameter increment with respect to age and therefore provides a more realistic height/diameter predictions using the coefficient of determination (R2), Mean Absolute Error (MAE) and Mean Square Error (MSE) results. The Kolmogorov-Smirnov test and Shapiro-Wilk test was also used to test the behavior of the error term for possible violations. The mean function of top height/Dbh over age using the two models under study predicted closely the observed values of top height/Dbh in the hyperbolic Richards nonlinear growth models better than the classical Richards growth model.

Keywords: height, diameter at breast height, DBH, hyperbolic sine function, Pinus caribaea, Richards' growth model

Procedia PDF Downloads 387
11135 Effect of Ethanolic Extract of Keladi Tikus (Typhonium flagelliforme) on the Level of Ifn Γ (Interferon Gamma), Vascular Endothelial Growth Factor (VEGF) and Caspase 3 Expression

Authors: Chodidjah, Edi Dharmana, Hardhono, Sarjadi

Abstract:

Breast cancer treatment options including surgery, radiation therapy, chemotherapy, and immunotherapy have not been effective. Besides, they have side effects. Keladi Tikus (Typhonium flagelliforme) has been shown to improve immune system, suppress tumor growth and induce apoptosis. One of the parameters for immune system, tumor growth and apoptosis is IFNγ (Interferon γ), VEGF (Vascular Endothelial Growth Factor) and Caspase 3 respectively. The aim of this study was to examine the effect of the administration of Keladi Tikus tuber extract at the dose of 200 mg/kgBW, 400 mg/KgBW, and 800 mg/kgBW on the level of IFNγ, VEGF and caspase 3 expression. In this experimental study using post test randomized control group design, 24 CH3 mice with tumor were randomly divided into 4 groups including control group and treated groups: Treated with 0.2 cc extract of Keladi Tikus at the dose of 200 mg/kgBW, 400 mg/kgBW, 800 mg/kgBW, respectively for 30 days. On day 31 the lymphatic tissue was taken and evaluated for its level of IFNγ, using ELISA. The tumor tissue was taken and subjected to immunohistochemistry staining for VEGF and caspase 3 expression evaluation. The data on IFNγ, VEGF and Caspase 3 expression were analyzed using One Way Anova with significant level of 0.05. One Way Anova resulted in p<0.05. LSD test showed that the level of IFNγ and Caspase 3 for control group was different from that of treated groups. There was no significant different between the treated group of 400 mg/KgBW and 800mg/KgBW. VEGF expressions for all the treated groups were significant. In conclusion, the oral administration of ethanolic extract of Keladi Tikus (Typhonium flagelliforme) at the dose of 200mg/kgBW, 400 mg/kgBW,800 mg/kgBW increases IFNγ, Caspase 3 and decreases VEGF expression in C3H mice with adenocarsinoma mamma.

Keywords: Typhonium flagelliforme, IFNγ, caspase 3, VEGF

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11134 Influence of the Reliability Index on the Safety Factor of the Concrete Contribution to Shear Strength of HSC Beams

Authors: Ali Sagiroglu, Sema Noyan Alacali, Guray Arslan

Abstract:

This paper presents a study on the influence of the safety factor in the concrete contribution to shear strength of high-strength concrete (HSC) beams according to TS500. In TS500, the contribution of concrete to shear strength is obtained by reducing diagonal cracking strength with a safety factor of 0.8. It was investigated that the coefficient of 0.8 considered in determining the contribution of concrete to the shear strength corresponds to which value of failure probability. Also, the changes in the reduction factor depending on different coefficients of variation of concrete were examined.

Keywords: reinforced concrete, beam, shear strength, failure probability, safety factor

Procedia PDF Downloads 825
11133 Estimation of PM2.5 Emissions and Source Apportionment Using Receptor and Dispersion Models

Authors: Swetha Priya Darshini Thammadi, Sateesh Kumar Pisini, Sanjay Kumar Shukla

Abstract:

Source apportionment using Dispersion model depends primarily on the quality of Emission Inventory. In the present study, a CMB receptor model has been used to identify the sources of PM2.5, while the AERMOD dispersion model has been used to account for missing sources of PM2.5 in the Emission Inventory. A statistical approach has been developed to quantify the missing sources not considered in the Emission Inventory. The inventory of each grid was improved by adjusting emissions based on road lengths and deficit in measured and modelled concentrations. The results showed that in CMB analyses, fugitive sources - soil and road dust - contribute significantly to ambient PM2.5 pollution. As a result, AERMOD significantly underestimated the ambient air concentration at most locations. The revised Emission Inventory showed a significant improvement in AERMOD performance which is evident through statistical tests.

Keywords: CMB, GIS, AERMOD, PM₂.₅, fugitive, emission inventory

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11132 Finite Element and Experimental Investigation of Ductile Crack Growth of Surface Cracks

Authors: Osama A. Terfas, Abdelhakim A. Hameda, Abdusalam A. Alktiwi

Abstract:

An investigation on ductile crack growth of shallow semi-elliptical surface cracks with a/w=0.2, a/c=0.33 under bending was carried out, where a is the crack depth, w is the plate thickness and c is the crack length at surface. Finite element analysis and experiments were modelling and the crack growth model were verified with experimental data. The results showed that the initial crack shape was no longer maintained as the crack developed under ductile tearing. The maximum growth at the deepest point at early stages was stopped when the crack depth reached half thickness and growth occurred beneath surface. Excellent agreement in the crack shape patterns was observed between the experiments and the crack growth model.

Keywords: crack growth, ductile tearing, mean stress, surface cracks

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11131 Facets of an Upcoming Urban Industrial Hub: A Case Study of Gurgaon-Manesar

Authors: Raman Kumar Singh

Abstract:

Urbanization and economic growth are considered to be the most striking features of the past century. There is currently a radical demographic shift in progress worldwide, wherein people are moving from rural to urban areas at an increasing rate. The UN-Habitat report 2005 indicates that in 2025, 61 per cent of the 5 billion world population will reside in the urban areas with about 85 per cent of the development process taking place in the urban hinterlands widely referred to as ‘peri-urban’, ‘suburbs’, ‘urban fringe’, ‘city edge’, ‘metropolitan shadow’, or ‘urban sprawl’. In this context the study is broadly concerned with understanding the development of the industrial hub in the Gurgaon and its impact on the immediate neighbourhood. However studies have revealed that with the increase of industrial development the growth pattern changes rapidly, not only the growth of the urban area but the overall economy shifts from more agrarian to non-agrarian, with the change in the occupational pattern of the people. The process is mainly known as tertiarization, where a number of tertiary activities increase in comparison to primary or secondary. The change in the occupational pattern creates a pull factor on its immediate neighbourhood, which triggers the in- migrations from the rural areas as people come in the core urban area in search of the better job opportunities and increased standards of living. But this gives way to the unplanned growth of the urban fringe and the villages which tend to accommodate the migrants and in turn the pressure on the socio-economic infrastructure increases. Therefore, it becomes increasing necessary for the government institution and policy level intervention to provide an overall socio-economic growth along with rapid industrial growth.

Keywords: policy intervention, urban morphology, urban industrial hub, livelihood transformation

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11130 Financial Inclusion from the Perspective of Social Innovation: The Case of Colombia

Authors: Maria Luisa Jaramillo, Alvaro Turriago Hoyos, Ulf Thoene

Abstract:

Financial inclusion has become a crucially important factor in debates on economic inequality posing challenges to the financial systems of countries around the world. Nowadays, governments and banks are concerned about creating products that allow access to wide sectors of the population. The creation of banking products by the financial sector for people with low incomes tends to lead to improvements in the quality of life of vulnerable parts of the population. In countries with notable social and economic inequalities financial inclusion is a key aspect for equitable economic growth. This study is based on the case of Colombia, which is a country with a strong record of economic growth over the past decade. Nevertheless, corruption, unemployment, and poverty contribute to uncertainty regarding the country’s future growth prospects. This study wants to explain the situation of financial exclusion and financial inclusion with respect to the Colombian case. Financial inclusion is going to be studied from the perspective of social innovation.

Keywords: Colombia, financial exclusion, financial inclusion, social innovation

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11129 First-Year Growth and Development of 445 Preterm Infants: A Clinical Study

Authors: Ying Deng, Fan Yang

Abstract:

Aim: To study the growth pattern of preterm infants during the first year of life and explore the association between head circumference (HC) and neurodevelopment sequences and to get a general knowledge of the incidence of anemia in preterm babies in Chengdu, Southwest China. Method: We conducted a prospective longitudinal study, neonates with gestational age < 37 weeks were enrolled this study from 2012.1.1 to 2014.7.9. Anthropometry (weight, height, HC) was obtained at birth, every month before 6 months-old and every 2 months in the next half year. All the infants’ age were corrected to 40 weeks. Growth data presented as Z-scores which was calculated by WHO Anthro software. Z-score defined as (the actual value minus the average value)/standard deviation. Neurodevelopment was assessed at 12 months-old [9-11 months corrected age (CA)] by using “Denver Development Screen Test (DDST)". The hemoglobin (Hb) was examined at 6 months for CA. Result: 445 preterm infants were followed-up 1 year, including 64 very low birth weight infants (VLBW), 246 low birth weight infants (LBW) and 135 normal birth weight infants(NBW). From full-term to 12 months after birth, catch-up growth was observed in most preterm infants. From VLBW to NBW, HCZ was -1.17 (95 % CI: -1.53,-0.80; P value < 0.0001) lower during the first12 months. WAZ was-1.12(95 % CI: -1.47,-0.76; p < 0.0001) lower. WHZ and HAZ were -1.04 (95%CI:-1.38, -0.69; P<0.0001) and -0.69 (95%CI:-1.06,-0.33; P < 0.0001) lower respectively. The peak of WAZ appeared during 0-3 months CA among preterm infants. For VLBW infants, the peak of HAZ and HCZ emerged at 8-11 months CA. However, the trend of HAZ and HCZ is the same as WAZ in LBW and NBW infants. Growth in the small for gestational age (SGA) infants was poorer than appropriate for gestational age (AGA) infants. The rate of DQ < 70 in VLBW and LBW were 29.6%, 7.7%, respectively (P < 0.0001). HCZ < -1SD at 3 months emerged as an independent predictor of DQ scores below 85 at 12 months after birth. The incidence of anemia in preterm infants was 11% at 6 months for CA. Moreover, 7 children (1.7%) diagnosed with Cerebral palsy (CP). Conclusions: The catch-up growth was observed in most preterm infants. VLBW and SGA showed poor growth. There was imbalance between WAZ and HAZ in VLBW infants. The VLBW babies had higher severe abnormal scores than LBW and NBW, especially in boys. Z score for HC at 3 months < -1SDwas a significant risk factor for abnormal DQ scores at the first year. The iron supplement reduced the morbidity of anemia in preterm infants.

Keywords: preterm infant, growth and development, DDST, Z-scores

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11128 Confirmatory Factor Analysis of Smartphone Addiction Inventory (SPAI) in the Yemeni Environment

Authors: Mohammed Al-Khadher

Abstract:

Currently, we are witnessing rapid advancements in the field of information and communications technology, forcing us, as psychologists, to combat the psychological and social effects of such developments. It also drives us to continually look for the development and preparation of measurement tools compatible with the changes brought about by the digital revolution. In this context, the current study aimed to identify the factor analysis of the Smartphone Addiction Inventory (SPAI) in the Republic of Yemen. The sample consisted of (1920) university students (1136 males and 784 females) who answered the inventory, and the data was analyzed using the statistical software (AMOS V25). The factor analysis results showed a goodness-of-fit of the data five-factor model with excellent indicators, as RMSEA-(.052), CFI-(.910), GFI-(.931), AGFI-(.915), TLI-(.897), NFI-(.895), RFI-(.880), and RMR-(.032). All within the ideal range to prove the model's fit of the scale’s factor analysis. The confirmatory factor analysis results showed factor loading in (4) items on (Time Spent), (4) items on (Compulsivity), (8) items on (Daily Life Interference), (5) items on (Craving), and (3) items on (Sleep interference); and all standard values of factor loading were statistically significant at the significance level (>.001).

Keywords: smartphone addiction inventory (SPAI), confirmatory factor analysis (CFA), yemeni students, people at risk of smartphone addiction

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11127 Obesity, Leptin Levels and Leptin Receptor Gene Polymorphisms in Afro-Caribbean Subjects

Authors: Lydia Foucan, Christine Rambhojan, Rachel Billy, Christophe Armand, Carl-Thony Michel, Jean-Marc Lacorte, Laurent Larifla

Abstract:

Leptin, an adipocyte-derived hormone, modulates insulin secretion and action via the leptin receptor (LEPR) that is expressed in pancreatic beta cells, adipose tissue, and muscle. Several polymorphisms have been described in the human LEPR gene including p.K109R (rs1137100), p.Q223R (rs1137101) and p.K656N (rs1805094) polymorphisms. The role of these polymorphisms is not yet studied in Guadeloupian population. Our aim was to explore the association of LEPR polymorphisms (K109R, Q223R and K656N) with leptin levels and obesity in non-diabetic Afro-Caribbean subjects. Genotypic analysis of the three polymorphisms was performed in 425 subjects using TaqMan and KASPar Assays. Serum leptin was measured with ELISA kits Biovendor® (RD191001100). Logistic regressions were used for assessment of statistical associations. Mean age was 47.6 ± 12.7 years. Among the participants, 238 (56 %) were women, 124 (30%) were obese and 155 (36.5%) had abdominal obesity. Carriers of LEPR K656N rs1805094 rare allele had significant higher frequencies of obesity (P = 0.007), abdominal obesity (P = 0.004) and metabolic syndrome (P = 0.021) but mean leptin level was not significantly different between both groups (P = 0.075). Odds ratios, adjusted for age and sex associated with presence of rs1805094 rare allele were 1.8 (1.1-2.9), P = 0.012 for obesity, 2.0 (1.2-3.3), P = 0.008 for abdominal obesity and 1.8 (1.1-3.0), P = 0.031 for MetS. No significant association was found with K109R, Q223R. These findings suggest that the K656N polymorphism (but not the K109R or Q223R polymorphism) of LEPR is associated with obesity, abdominal obesity and metabolic syndrome in this Afro-Caribbean non-diabetic population.

Keywords: Afro-Caribbean, leptin levels, leptin receptor gene polymorphisms, obesity

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11126 Using Eigenvalues and Eigenvectors in Population Growth and Stability Obtaining

Authors: Abubakar Sadiq Mensah

Abstract:

The Knowledge of the population growth of a nation is paramount to national planning. The population of a place is studied and a model developed over a period of time, Matrices is used to form model for population growth. The eigenvalue ƛ of the matrix A and its corresponding eigenvector X is such that AX = ƛX is calculated. The stable age distribution of the population is obtained using the eigenvalue and the characteristic polynomial. Hence, estimation could be made using eigenvalues and eigenvectors.

Keywords: eigenvalues, eigenvectors, population, growth/stability

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11125 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function

Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

Abstract:

This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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11124 Preservation of Phenytoin and Sodium Valproate Induced Bone Loss by Raloxifene through Modulating Serum Estradiol and TGF-β3 Content in Bone of Female Mice

Authors: Divya Vohora, Md. Jamir Anwar

Abstract:

Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. Both phenytoin (PHT) and sodium valproate (SVP) inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with CVD supplementation, on PHT and SVP-induced alterations in bone in mice. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of AEDs was also investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and curative treatment with raloxifene ameliorated bony alterations and was more effective than CVD. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with their antiepileptic efficacy, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Keywords: antiepileptic drugs, osteoporosis, raloxifene, TGF-β3

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11123 The External Debt in the Context of Economic Growth: The Sample of Turkey

Authors: Ayşen Edirneligil, Mehmet Mucuk

Abstract:

In developing countries, one of the most important restrictions about the economic growth is the lack of national savings which are supposed to finance the investments. In order to overcome this restriction and achieve the higher rate of economic growth by increasing the level of output, countries choose the external borrowing. However, there is a dispute in the literature over the correlation between external debt and economic growth. The aim of this study is to examine the effects of external debt on Turkish economic growth by using VAR analysis with the quarterly data over the period of 2002:01-2014:04. In this respect, Johansen Cointegration Test, Impulse- Response Function and Variance Decomposition Tests will be used for analyses. Empirical findings show that there is no cointegration in the long run.

Keywords: external debt, economic growth, Turkish economy, time series analysis

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11122 Microstructure Dependent Fatigue Crack Growth in Aluminum Alloy

Authors: M. S. Nandana, K. Udaya Bhat, C. M. Manjunatha

Abstract:

In this study aluminum alloy 7010 was subjected to three different ageing treatments i.e., peak ageing (T6), over-ageing (T7451) and retrogression and re ageing (RRA) to study the influence of precipitate microstructure on the fatigue crack growth rate behavior. The microstructural modification was studied by using transmission electron microscope (TEM) to examine the change in the size and morphology of precipitates in the matrix and on the grain boundaries. The standard compact tension (CT) specimens were fabricated and tested under constant amplitude fatigue crack growth tests to evaluate the influence of heat treatment on the fatigue crack growth rate properties. The tests were performed in a computer-controlled servo-hydraulic test machine applying a load ratio, R = 0.1 at a loading frequency of 10 Hz as per ASTM E647. The fatigue crack growth was measured by adopting compliance technique using a CMOD gauge attached to the CT specimen. The average size of the matrix precipitates were found to be of 16-20 nm in T7451, 5-6 nm in RRA and 2-3 nm in T6 conditions respectively. The grain boundary precipitate which was continuous in T6, was disintegrated in RRA and T7451 condition. The PFZ width was lower in RRA compared to T7451 condition. The crack growth rate was higher in T7451 and lowest in RRA treated alloy. The RRA treated alloy also exhibits an increase in threshold stress intensity factor range (∆Kₜₕ). The ∆Kₜₕ measured was 11.1, 10.3 and 5.7 MPam¹/² in RRA, T6 and T7451 alloys respectively. The fatigue crack growth rate in RRA treated alloy was nearly 2-3 times lower than that in T6 and was one order lower than that observed in T7451 condition. The surface roughness of RRA treated alloy was more pronounced when compared to the other conditions. The reduction in fatigue crack growth rate in RRA alloy was majorly due to the increase in roughness and partially due to increase in spacing between the matrix precipitates. The reduction in crack growth rate and increase in threshold stress intensity range is expected to benefit the damage tolerant capability of aircraft structural components under service loads.

Keywords: damage tolerance, fatigue, heat treatment, PFZ, RRA

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11121 Comparative Efficacy of Angiotensin Converting Enzymes Inhibitors and Angiotensin Receptor Blockers in Patients with Heart Failure in Tanzania: A Prospective Cohort Study

Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

Abstract:

Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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11120 Effect of Different Commercial Diets and Temperature on the Growth Performance, Feed Intake and Feed Conversion Ratio of Sobaity Seabream Sparidentex hasta

Authors: Seemab Zehra, A. H. W. Mohammed, E. Pantanella, J. L. Q. Laranja, P. H. De Mello, R. Saleh, A. A. Siddik, A. Al Shaikhi, A. M. Al-Suwailem

Abstract:

Two separate feeding trials were conducted to determine the effects of using different commercial diets and water temperatures on the growth performance, feed intake, feed conversion ratio (FCR) and condition factor of sobaity seabream Sparidentex hasta. In experiment I, growth performance, feed intake, protein efficiency ratio (PER), feed conversion ratio (FCR) and survival (%) of sobaity seabream Sparidentex hasta (330.5±2.6 g; 26.9±1.0 cm) were evaluated by four different commercial diets (1, 2, 3 and 4) for 80 days. The daily weight gain was around 3.2 g day-1 with an SGR of 0.7% day-1. Both the FCR and PER in the fish were significantly better in diet 2 that contained 46.36% crude protein and 12.54% crude fat. In experiment II, (99±2.6 g; 17.1±1.0 cm). The fish were cultured in 1m3 tanks supplied with seawater from the Red Sea wherein three different rearing temperatures were set as treatments (24, 28 and 32°C). Fish were fed with a commercial diet based on the results of experiment I (46.4% protein; 20.1 MJ kg-1 energy) to satiation for 96 days. Total weight gain was significantly higher for the fish reared in the 32°C group (158.57 g) followed by the 28°C group (138.25 g), while the lowest weight gain was observed in the 24°C group (116.98 g). The FCR was significantly lower in the 32°C group (1.62) as compared to 28 (1.8) and 24°C (1.85) groups. Based on the results obtained from these preliminary studies (experiment I and II), sobaity seabream can attain better growth performance, FCR and PER at 32°C in the Red Sea by feeding commercial diet 2.

Keywords: Sparidentex hasta, nutrition, FCR, Red Sea, growth performance

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11119 Identification of Conserved Domains and Motifs for GRF Gene Family

Authors: Jafar Ahmadi, Nafiseh Noormohammadi, Sedegeh Fabriki Ourang

Abstract:

GRF, Growth regulating factor, genes encode a novel class of plant-specific transcription factors. The GRF proteins play a role in the regulation of cell numbers in young and growing tissues and may act as transcription activations in growth and development of plants. Identification of GRF genes and their expression are important in plants to performance of the growth and development of various organs. In this study, to better understanding the structural and functional differences of GRFs family, 45 GRF proteins sequences in A. thaliana, Z. mays, O. sativa, B. napus, B. rapa, H. vulgare, and S. bicolor, have been collected and analyzed through bioinformatics data mining. As a result, in secondary structure of GRFs, the number of alpha helices was more than beta sheets and in all of them QLQ domains were completely in the biggest alpha helix. In all GRFs, QLQ, and WRC domains were completely protected except in AtGRF9. These proteins have no trans-membrane domain and due to have nuclear localization signals act in nuclear and they are component of unstable proteins in the test tube.

Keywords: domain, gene family, GRF, motif

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11118 Impact of Foreign Direct Investment to the Economic Growth of Rwanda

Authors: Munezero Vanessa

Abstract:

A country is considered developed when its socio-economic and development situation is stable. Foreign direct investment is thus considered to be one of the solutions to this stability especially when it is used in development sectors. The present study was meant to understand whether the foreign direct investment stimulates economic growth performance in Rwanda. The foreign direct investments and economic growth (GDP) has been the subject of much debate among economic development researchers, aid donors as well as recipients in general and Rwanda in particular. In spite of this, there are only few empirical studies that investigate the contributions of foreign direct investments to economic growth in Rwanda. This study explores the relationship between foreign direct investments and economic growth in Rwanda using data that spans from 2000 to 2019 and establishing through causal study if changes in one variable cause changes in the other. The results show that foreign direct investments significantly contribute to the current level of economic growth. The findings imply that Rwanda could enhance its economic growth by effectively and strategically strengthening foreign direct investment plans.

Keywords: foreign direct investment (FDI), economic growth, GDP gross domestic product (GDP), inflation, exchange rate

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11117 Women in Higher Education in Nigeria: A Panacea for Developmental Growth

Authors: Lucy Adesomon Okukpon, Margaret Omolara Akerele

Abstract:

Higher Education in Nigeria is sought after by women, they believe that the economic power and growth lies in the attainment and pursuit of higher Education. No nation in the world can boast of developmental growth when the women are not fully empowered educationally. The attainment of higher education spurs women to contribute meaningfully towards the growth and development of the Nigerian workforce. Recent innovations and trends reveal that over fifty per cent of Nigerian women have attained higher education within and outside the country. Women in Nigeria have expressed their growing concern of what becomes of the remaining 50 per cent who are unable to attain basic education. This concern has brought about the issue of funding which is a practical challenge towards the attainment of education for these vulnerable women. Another challenging factor is that most women often seek the permission of their husbands, brothers, fathers and uncles to enable them attain educational pursuit, especially when the institution is miles away from their place of abode. The solution to this problems from research findings reveal that the umbrella body which co-ordinates education for women in Nigeria (The National Council of Women Societies, NCWS) have taken it upon itself to provide educational learning centres in all the states of the Federation including Abuja the Nations capital city. This is to stem the ugly trend and enable women gain access to educational facilities provided for their growth and development. This positive stride has brought succour to women who hitherto have no hope of attaining any form of education. Moreover, awareness creation concerning higher education is translated into different Nigerian languages so that the women at the grassroots can benefit immensely and contribute towards the growth and development of the Nation. Their educational progress attest to the fact that Nigerian Women are happy for the educational opportunities provided and have vowed to attain greater heights particularly where higher education is concerned.

Keywords: developmental growth, educational attainment, higher education, women in higher education, Nigeria

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11116 Characterization of Calcium-Signalling Mediated by Human GPR55 Expressed in HEK293 Cells

Authors: Yousuf M. Al Suleimani, Robin Hiley

Abstract:

The endogenous phospholipid lysophosphatidylinositol (LPI) was recently identified as a novel ligand for the G protein-coupled receptor 55 (GPR55) and an inducer of intracellular Ca2+ [Ca2+]i release. This study attempts to characterize Ca2+ signals provoked by LPI in HEK293 cells engineered to stably express human GPR55 and to test cannabinoid ligand activity at GPR55. The study shows that treatment with LPI stimulates a sustained, oscillatory Ca2+ release. The response is characterized by an initial rapid rise, which is mediated by the Gαq-PLC-IP3 pathway, and this is followed by prolonged oscillations that require RhoA activation. Ca2+ oscillations are initiated by intracellular mechanisms and extracellular Ca2+ is only required to replenish Ca2+ lost from the cytoplasm. Analysis of cannabinoid ligand activity at GPR55 revealed no clear effect of the endocannabinoid anandamide, however, rimonabant and the CB1 receptor antagonist AM251 evoked GPR55-mediated [Ca2+]i. Thus, LPI is likely to be a key plasma membrane mediator of signaling events and changes in gene expression through GPR55 activation.

Keywords: lysophosphatidylinositol, calcium, GPR55, cannabinoid

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11115 Association between TNF-α and Its Receptor TNFRSF1B Polymorphism with Pulmonary Tuberculosis in Tomsk, Russia Federation

Authors: K. A. Gladkova, N. P. Babushkina, E. Y. Bragina

Abstract:

Purpose: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the major public health problems worldwide. It is clear that the immune response to M. tuberculosis infection is a relationship between inflammatory and anti-inflammatory responses in which Tumour Necrosis Factor-α (TNF-α) plays key roles as a pro-inflammatory cytokine. TNF-α involved in various cell immune responses via binding to its two types of membrane-bound receptors, TNFRSF1A and TNFRSF1B. Importantly, some variants of the TNFRSF1B gene have been considered as possible markers of host susceptibility to TB. However, the possible impact of such TNF-α and its receptor genes polymorphism on TB cases in Tomsk is missing. Thus, the purpose of our study was to investigate polymorphism of TNF-α (rs1800629) and its receptor TNFRSF1B (rs652625 and rs525891) genes in population of Tomsk and to evaluate their possible association with the development of pulmonary TB. Materials and Methods: The population distribution features of genes polymorphisms were investigated and made case-control study based on group of people from Tomsk. Human blood was collected during routine patients examination at Tomsk Regional TB Dispensary. Altogether, 234 TB-positive patients (80 women, 154 men, average age is 28 years old) and 205 health-controls (153 women, 52 men, average age is 47 years old) were investigated. DNA was extracted from blood plasma by phenol-chloroform method. Genotyping was carried out by a single-nucleotide-specific real-time PCR assay. Results: First, interpopulational comparison was carried out between healthy individuals from Tomsk and available data from the 1000 Genomes project. It was found that polymorphism rs1800629 region demonstrated that Tomsk population was significantly different from Japanese (P = 0.0007), but it was similar with the following Europeans subpopulations: Italians (P = 0.052), Finns (P = 0.124) and British (P = 0.910). Polymorphism rs525891 clear demonstrated that group from Tomsk was significantly different from population of South Africa (P = 0.019). However, rs652625 demonstrated significant differences from Asian population: Chinese (P = 0.03) and Japanese (P = 0.004). Next, we have compared healthy individuals versus patients with TB. It was detected that no association between rs1800629, rs652625 polymorphisms, and positive TB cases. Importantly, AT genotype of polymorphism rs525891 was significantly associated with resistance to TB (odds ratio (OR) = 0.61; 95% confidence interval (CI): 0.41-0.9; P < 0.05). Conclusion: To the best of our knowledge, the polymorphism of TNFRSF1B (rs525891) was associated with TB, while genotype AT is protective [OR = 0.61] in Tomsk population. In contrast, no significant correlation was detected between polymorphism TNF-α (rs1800629) and TNFRSF1B (rs652625) genes and alveolar TB cases among population of Tomsk. In conclusion, our data expands the molecular particularities associated with TB. The study was supported by the grant of the Russia for Basic Research #15-04-05852.

Keywords: polymorphism, tuberculosis, TNF-α, TNFRSF1B gene

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11114 The Influence of Crude Oil on Growth of Freshwater Algae

Authors: Al-Saboonchi Azhar

Abstract:

The effects of Iraqi crude oil on growth of three freshwater algae (Chlorella vulgaris Beij., Scenedesmus acuminatus (Lag.) Chodat. and Oscillatoria princeps Vauch.) were investigated, basing on it's biomass expressed as Chl.a. Growth rate and doubling time of the cell were calculated. Results showed that growth rate and species survival varied with concentrations of crude oil and species type. Chlorella vulgaris and Scenedesmus acuminatus were more sensitive in culture containing crude oil as compared with Oscillatoria princeps cultures. The growth of green algae were significantly inhibited in culture containing (5 mg/l) crude oil, while the growth of Oscillatoria princeps reduced in culture containing (10 mg/l) crude oil.

Keywords: algae, crude oil, green algae, Cyanobacteria

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11113 Critical Study on the Sensitivity of Corrosion Fatigue Crack Growth Rate to Cyclic Waveform and Microstructure in Marine Steel

Authors: V. C. Igwemezie, A. N. Mehmanparast

Abstract:

The primary focus of this work is to understand how variations in the microstructure and cyclic waveform affect the corrosion fatigue crack growth (CFCG) in steel, especially in the Paris region of the da/dN vs. ΔK curve. This work is important because it provides fundamental information on the modelling, design, selection, and use of steels for various engineering applications in the marine environment. The corrosion fatigue tests data on normalized and thermomechanical control process (TMCP) ferritic-pearlitic steels by the authors were compared with several studies on different microstructures in the literature. The microstructures of these steels are radically different and general comparative fatigue crack growth resistance performance study on the effect of microstructure in these materials are very scarce and where available are limited to few studies. The results, for purposes of engineering application, in this study show less dependency of fatigue crack growth rate (FCGR) on yield strength, tensile strength, ductility, frequency and stress ratio in the range 0.1 – 0.7. The nature of the steel microstructure appears to be a major factor in determining the rate at which fatigue cracks propagate in the entire da/dN vs. ΔK sigmoidal curve. The study also shows that the sine wave shape is the most damaging fatigue waveform for ferritic-pearlitic steels. This tends to suggest that the test under sine waveform would be a conservative approach, regardless of the waveform for design of engineering structures.

Keywords: BS7910, corrosion-fatigue crack growth rate, cyclic waveform, microstructure, steel

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11112 Motherhood Factors Influencing the Business Growth of Women-Owned Sewing Businesses in Lagos, Nigeria: A Mixed Method Study

Authors: Oyedele Ogundana, Amon Simba, Kostas Galanakis, Lynn Oxborrow

Abstract:

The debate about factors influencing the business growth of women-owned businesses has been a topical issue in business management. Currently, scholars have identified the issues of access to money, market, and management as canvasing factors influencing the business growth of women-owned businesses. However, the influence of motherhood (household/family context) on business growth is inconclusive in the literature; despite that women are more family-oriented than their male counterparts. Therefore, this research study considers the influence of motherhood factor (household/family context) on the business growth of women-owned sewing businesses (WOSBs) in Lagos, Nigeria. The sewing business sector is chosen as the fashion industry (which includes sewing businesses) currently accounts for the second largest number of jobs in Sub-Saharan Africa, following agriculture. Thus, sewing businesses provide a rich ground for contributing to existing scholarly work. Research questions; (1) In what way does the motherhood factor influence the business growth of WOSBs in Lagos? (2) To what extent does the motherhood factor influence the business growth of WOSBs in Lagos? For the method design, a pragmatic approach, a mixed-methods technique and an abductive form of reasoning are adopted. The method design is chosen because it fits, better than other research perspectives, with the research questions posed in this study. For instance, using a positivist approach will not sufficiently answer research question 1, neither will an interpretive approach sufficiently answer research question 2. Therefore, the research method design is divided into 2 phases, and the results from one phase are used to inform the development of the subsequent phases (only phase 1 has been completed at the moment). The first phase uses qualitative data and analytical method to answer research question 1. While the second phase of the research uses quantitative data and analytical method to answer research question 2. For the qualitative phase, 5 WOSBs were purposefully selected and interviewed. The sampling technique is selected as it was not the intention of the researcher to make any statistical inferences, at this phase, rather the purpose was just exploratory. Therefore, the 5 sampled women comprised of 2 unmarried women, 1 married woman with no child, and 2 married women with children. A 40-60 minutes interview was conducted per participants. The interviews were audio-recorded and transcribed. Thereafter, the data were analysed using thematic analysis in order to unearth patterns and relationships. Findings for the first phase of this research reveals that motherhood (household/family context) directly influences (positively/negatively) the performance of WOSBs in Lagos. Apart from a direct influence on WOSBs, motherhood also moderates (positively/negatively) other factors–e.g., access to money, management/human resources and market/opportunities– influencing WOSBs in Lagos. To further strengthen this conclusion, a word frequency query result shows that ‘family,’ ‘husband’ and ‘children’ are among the 10 words used frequently in all the interview transcripts. This first phase contributes to existing studies by showing the various forms by which motherhood influences WOSBs. The second phase (which data are yet to be collected) would reveal the extent to which motherhood influence the business growth of WOSBs in Lagos.

Keywords: women-owned sewing businesses, business growth, motherhood, Lagos

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