Search results for: epidermal growth factor receptor

Authors: Mariam Khaled, Noha Farag, Ghada Mohamed Abdel Salam, Khaled Abu-Aisha, Mohamed El-Azizi

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Gastric and colorectal cancers are among the most frequent causes of cancer-associated mortalities in Africa. They have been considered as a global public health concern, as nearly one million new cases are reported per year. IL-1β is a pro-inflammatory cytokine-produced by activated macrophages and monocytes- and a member of the IL-1 family. The inactive IL-1β precursor is cleaved and activated by caspase-1 enzyme, which itself is activated by the assembly of intracellular structures defined as NLRP3 (Nod Like receptor P3) inflammasomes. Activated IL-1β stimulates the Interleukin-1 receptor type-1 (IL-1R1), which is responsible for the initiation of a signal transduction pathway leading to cell proliferation. It has been proven that the IL-1β gene is a highly polymorphic gene in which single nucleotide polymorphisms (SNPs) may affect its expression. It has been previously reported that SNPs including base transitions between C and T at positions, -511 (C-T; dbSNP: rs16944) and -31 (C-T; dbSNP: rs1143627), from the transcriptional start site, contribute to the pathogenesis of gastric and colorectal cancers by affecting IL-1β levels. Altered production of IL-1β due to such polymorphisms is suspected to stimulate an amplified inflammatory response and promote Epithelial Mesenchymal Transition leading to malignancy. Allele frequency distribution of the IL-1β-31 and -511 SNPs, in different populations, and their correlation to the incidence of gastric and colorectal cancers, has been intriguing to researchers worldwide. The current study aims to investigate allele distributions of the IL-1β SNPs among gastric and colorectal cancers Egyptian patients. In order to achieve to that, 89 Biopsy and surgical specimens from the antrum and corpus mucosa of chronic gastritis subjects and gastric and colorectal carcinoma patients was collected for DNA extraction followed by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). The amplified PCR products of IL-1β-31C > T and IL-1β-511T > C were digested by incubation with the restriction endonuclease enzymes ALu1 and Ava1. Statistical analysis was carried out to determine the allele frequency distribution in the three studied groups. Also, the effect of the IL-1β -31 and -511 SNPs on nuclear factor binding was analyzed using Fluorescence Electrophoretic Mobility Shift Assay (EMSA), preceded by nuclear factor extraction from gastric and colorectal tissue samples and LPS stimulated monocytes. The results of this study showed that a significantly higher percentage of Egyptian gastric cancer patients have a homozygous CC genotype at the IL-1β-31 position and a heterozygous TC genotype at the IL-1β-511 position. Moreover, a significantly higher percentage of the colorectal cancer patients have a homozygous CC genotype at the IL-1β-31 and -511 positions as compared to the control group. In addition, the EMSA results showed that IL-1β-31C/T and IL-1β-511T/C SNPs do not affect nuclear factor binding. Results of this study suggest that the IL-1β-31 C/T and IL-1β-511 T/C may be correlated to the incidence of gastric cancer in Egyptian patients; however, similar findings couldn’t be proven in the colorectal cancer patients group for the IL-1β-511 T/C SNP. This is the first study to investigate IL-1β -31 and -511 SNPs in the Egyptian population.

Keywords: colorectal cancer, Egyptian patients, gastric cancer, interleukin-1β, single nucleotide polymorphisms

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Authors: Jiang Xu, Daoping Wang, Yinghong Pan

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The jointing-booting stage is a critical period of both vegetative growth and reproductive growth in rice. Therefore, the proteomic analysis of the mutant Osbri1, whose corresponding gene OsBRI1 encodes the putative BRs receptor OsBRI1, at jointing-booting stage is very important for understanding the effects of BRs on vegetative and reproductive growth. In this study, the proteomes of leaves from an allelic mutant of the DWARF 61 (D61, OsBRI1) gene, Fn189 (dwarf54, d54) and its wild-type variety T65 (Taichung 65) at jointing-booting stage were analysed by using a Q Exactive plus orbitrap mass spectrometer, and more than 3,100 proteins were identified in each sample. Ontology analysis showed that these proteins distribute in various space of the cells, such as the chloroplast, mitochondrion, and nucleus, they functioned as structural components and/or catalytic enzymes and involved in many physiological processes. Moreover, quantitative analysis displayed that 266 proteins were differentially expressed in two samples, among them, 77 proteins decreased and 189 increased more than two times in Fn189 compared with T65, the proteins whose content decreased in Fn189 including b5-like Heme/Steroid binding domain containing protein, putative retrotransposon protein, putative glutaminyl-tRNA synthetase, and higher content proteins such as mTERF, putative Oligopeptidase homologue, zinc knuckle protein, and so on. A former study founded that the transcription level of a mTERF was up-regulated in the leaves of maize seedling after EBR treatment. In our experiments, it was interesting that one mTERF protein increased, but another mTERF decreased in leaves of Fn189 at jointing-booting stage, which suggested that BRs may have differential regulation mechanisms on the expression of various mTERF proteins. The relationship between other differential proteins with BRs is still unclear, and the effects of BRs on rice protein contents and its regulation mechanisms still need further research.

Keywords: bri1 mutant, jointing-booting stage, proteomic analysis, rice

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Authors: Sachin K. Samuchiwal, Barbara Balestrieri, Amanda Paskavitz, Hannah Raff, Joshua A. Boyce

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IL-33, a recently discovered member of the IL-1 cytokine family, binds to the TLR/IL1R super family receptor ST2 and induces type 2 immune responses. IL-33 is constitutively expressed in structural cells at barrier sites such as skin, lung, and intestine, and also inducibly expressed by hematopoietic cells including macrophages. Stimulation of macrophages by Lipopolysaccharide (LPS) can induce de novo IL-33 expression, and also causes the production of prostaglandin-E2 (PGE2) via cyclooxygenase (COX)-2 and microsomal PGE2 synthase-1 (mPGES-1). Because PGE2 can regulate macrophage functions through both autocrine and paracrine mechanisms, the potential interplay of endogenous PGE2 on IL-33 production was explored. Bone-marrow derived murine macrophages (bmMF) that lack either mPGES-1 or EP2 receptor expression were stimulated with LPS in the absence or presence of exogenous PGE2 along with pharmacological agonists and antagonists. The study results demonstrate that endogenous PGE2 markedly enhances LPS-induced IL-33 production by bmMFs via EP2 receptors. Moreover, exogenous PGE2 can amplify LPS-induced IL-33 expression dominantly by EP2 and partly by EP4 receptors by a pathway involving cAMP and exchange protein activated by cAMP (EPAC), but not protein kinase A (PKA). Though both IL-33 production and PGE2 generation in response to LPS require activation of both p38 MAPK and NF-κB, PGE2 did not influence this activation. In conclusion, it is demonstrated that endogenous PGE2 signaling through EP2 and EP4 receptors is a prerequisite for LPS-induced IL-33 production in bmMFs and the underlying cAMP mediated pathway involves EPAC. Since IL-33 is a critical pro-inflammatory cytokine in various pathological disorders, this PGE2-EP2/EP4-cAMP mediated pathway can be exploited to intervene in IL-33 driven pathologies.

Keywords: bone marrow macrophages, EPAC, IL-33, PGE2

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Authors: Muslim Idan Mohsin, Mohammed Jasim Al-Shamarti, Rusul Idan Mohsin, Ali A. Majeed

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One of the causative agents of the lower respiratory tract (LRT) is Pseudomonas aeruginosa, which can lead to severe infection associated with a lung infection. There are many cytokines that are secreted in response to bacterial infection, in particular interleukin IL-36 cytokine in response to P. aeruginosa infection. The involvement of IL-36 in the P. aeruginosa infection could be a clue to find a specific way for treatments of different inflammatory and degenerative lung diseases. IL36 promotes primary immune response via binding to the IL-36 receptor (IL-36R). Indeed, an overactivity of IL-36 might be an initiating factor for many immunopathologic sceneries in pneumonia. Here we demonstrate if the IL-36 cytokine increases in response P. aeruginosa infection that is isolated from lower respiratory tract infection (LRT). We demonstrated that IL-36 expression significantly unregulated in human lung epithelial (A549) cells after infected by P. aeruginosa at mRNA level.

Keywords: IL36, Pseudomonas aeruginosa, LRT infection, A549 cells

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Authors: Roikhan Mochamad Aziz

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This study aims to analze the interdependence of several variables simultaneously in order to simplify the form of the relationship between some of the variables studied a number of factors less than the variable studied which means it can also describe the data structure of a research. Based 100 respondents from the public, such as the people of South Tangerang, this study used factor analysis tool. The results of this study indicate that the studied variables being formed into nine factors, namely faith factors, community factors, factors of social care, confidence factor, factor income, educational factors, self-satisfaction factors, factors work, and knowledge factor. Total variance of the 9 factors is 67,30% means that all nine of these factors are factors that can contribute too paying zakat of muzakki consciousness of 67,30% while the remaining 32,70% is supported by other factors outside the 9 factors.

Keywords: zakat, analysis factor, faith, education, knowledge

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Authors: Dileep Kumar, Janhavi Ramchandra Rao Kumar, Rao

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COVID-19 has ravaged the globe, and it is spreading its Spectre day by day. In the absence of established drugs, this disease has created havoc. Some of the infected persons are symptomatic or asymptomatic. The respiratory system, cardiac system, digestive system, etc. in human beings are affected by this virus. In our present investigation, we have undertaken a study of the Indian Ayurvedic herb, Ocimum sanctum against SARS-CoV-2 using molecular docking and dynamics studies. The docking analysis was performed on the Glide module of Schrödinger suite on two different proteins from SARS-CoV-2 viz. NSP15 Endoribonuclease and spike receptor-binding domain. MM-GBSA based binding free energy calculations also suggest the most favorable binding affinities of carvacrol, β elemene, and β caryophyllene with binding energies of −61.61, 58.23, and −54.19 Kcal/mol respectively with spike receptor-binding domain and NSP15 Endoribonuclease. It rekindles our hope for the design and development of new drug candidates for the treatment of COVID19.

Keywords: molecular docking, COVID-19, ocimum sanctum, binding energy

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Authors: Abigail Mosetsanagape Mooketsi, Itumeleng Pleasure Mongale, Joel Hinaunye Eita

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The aim of this study is to analyse the impact of transport infrastructure on economic growth in South Africa through Engle Granger two step approach using the data from 1970 to 2013. GDP is used as a proxy for economic growth whilst rail transport (rail lines, rail goods transported) and air transport(air passengers carried, air freight) are used as proxies for transport infrastructure. The results showed that there is a positive long-run relationship between transport infrastructure and economic growth. The results show that South Africa’s economic growth can be boosted by providing transport infrastructure. The estimated models were simulated and the results that the model is a good fit. The findings of this research will be beneficial to policy makers, academics and it will also enhance the ability of the investors to make informed decisions about investing in South Africa.

Keywords: transport, infrastructure, economic growth, South Africa

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Authors: Souhir Ben Amor, Heni Boubaker, Lotfi Belkacem

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This aims of this paper is to forecast the electricity spot prices. First, we focus on modeling the conditional mean of the series so we adopt a generalized fractional -factor Gegenbauer process (k-factor GARMA). Secondly, the residual from the -factor GARMA model has used as a proxy for the conditional variance; these residuals were predicted using two different approaches. In the first approach, a local linear wavelet neural network model (LLWNN) has developed to predict the conditional variance using the Back Propagation learning algorithms. In the second approach, the Gegenbauer generalized autoregressive conditional heteroscedasticity process (G-GARCH) has adopted, and the parameters of the k-factor GARMA-G-GARCH model has estimated using the wavelet methodology based on the discrete wavelet packet transform (DWPT) approach. The empirical results have shown that the k-factor GARMA-G-GARCH model outperform the hybrid k-factor GARMA-LLWNN model, and find it is more appropriate for forecasts.

Keywords: electricity price, k-factor GARMA, LLWNN, G-GARCH, forecasting

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Authors: Zahra Amirhosseini, Mahtab Nameni

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The aim of this study was to investigate the relationship between growth, beta, and Company's cash. We calculate cash as dependent variable and growth opportunity and beta as independent variables. This study was based on an analysis of panel data. Population of the study is the companies which listed in Tehran Stock exchange and a financial data of 215 companies during the period 2010 to 2015 have been selected as the sample through systematic sampling. The results of the first hypothesis showed there is a significant relationship between growth opportunities cash holdings. Also according to the analysis done in the second hypothesis, we determined that there is an inverse relation between company risk and cash holdings.

Keywords: growth, beta, liquidity, company

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Authors: Givi Kupatadze

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Backward economies are facing a challenge of achieving sustainable high economic growth rate. Dominant growth models represent a roadmap in framing economic development strategy. This paper examines a relevance of the dominant growth models for backward economies. Cobb-Douglas production function, the Harrod-Domar model of economic growth, the Solow growth model and general formula of gross domestic product are examined to undertake a comprehensive study of the dominant growth models. Deductive research method allows to uncover major weaknesses of the dominant growth models and to come up with practical implications for economic development strategy. The key finding of the paper shows, contrary to what used to be taught by textbooks of economics, that constant returns to scale property of the dominant growth models are a mere coincidence and its generalization over space and time can be regarded as one of the most unfortunate mistakes in the whole field of political economy. The major suggestion of the paper for backward economies is that understanding and considering taxonomy of economic activities based on increasing and diminishing returns to scale represent a cornerstone of successful economic development strategy.

Keywords: backward economies, constant returns to scale, dominant growth models, taxonomy of economic activities

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Authors: Susmita Ghosh, Bhaskar Bhowmick

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Market is an important factor for start-ups to look into during decision-making in product development and related areas. Emerging country markets are more uncertain in terms of information availability and institutional supports. The literature review of market uncertainty reveals the need for identifying factors representing the market uncertainty. This paper identifies factors for market uncertainty using Exploratory Factor Analysis (EFA) and confirms the number of factor retention using an alternative factor retention criterion, ‘Parallel Analysis’. 500 entrepreneurs, engaged in start-ups from all over India participated in the study. This paper concludes with the factor structure of ‘market uncertainty’ having dimensions of uncertainty in industry orientation, uncertainty in customer orientation and uncertainty in marketing orientation.

Keywords: uncertainty, market, orientation, competitor, demand

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Authors: Hamzeh Dodeen

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This study aims at examining the effects of item wording effects on the factor structure of the University of California, Los Angeles (UCLA) Loneliness Scale: gender, age, and marital status differences. A total of 2374 persons from the UAE participated, representing six different populations (teenagers/elderly, males/females, and married/unmarried). The results of the exploratory factor analysis using principal axis factoring with (oblique) rotation revealed that two factors were extracted from the 20 items of the scale. The nine positively worded items were highly loaded on the first factor, while 10 out of the 11 negatively worded items were highly loaded on the second factor. The two-factor solution was confirmed on the six different populations based on age, gender, and marital status. It has been concluded that the rating of the UCLA scale is affected by a response style related to the item wording.

Keywords: UCLA Loneliness Scale, loneliness, positively worded items, factor structure, negatively worded items

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Authors: Kittitara Chunlakittiphan, Patompong Satapornpong

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Introduction: The variation of genetics affects how our body responds to pharmaceuticals elucidates the correlation between long-term use of medical cannabis and adverse drug reactions (ADRs). Medical cannabis is regarded as the treatment for chronic pain, cancer pain, acute pain, psychological disorders, multiple sclerosis and migraine management. However, previous studies have shown that delta-9-Tetrahydrocannabinol (THC), an ingredient found in cannabis, was the cause of ADRs in CB1 receptors found in humans. Previous research suggests that distributions of the cannabinoid type 1 (CB1) receptor gene and pharmacogenetic markers, which vary amongst different populations, might affect incidences of ADRs. Although there is an evident need to investigate the level of the CB1 receptor gene (rs806365), studies on the distribution of CB1-pharmacogenetics markers in Thai patients are limited. Objective: Therefore, the aim of this study is to investigate the distribution of the rs806365 polymorphism in Thai patients who have been treated with medical cannabis. Materials and Methods: We enrolled 31 Thai patients with THC-induced ADRs and 34 THC-tolerant controls to take part in this study. All patients with THC-induced ADRs were accessed through a review of medical records by physicians. EDTA blood of 3ml was collected to obtain the CNR1 gene (rs806365) and genotyping of this gene was conducted using the real-time PCR ViiA7 (ABI, Foster City, CA, USA) following the manufacturer’s instruction. Results: The sample consisted of 65 patients (40/61.54%) were females and (25/38.46%) were males, with an age range of 19-87 years, who have been treated with medical cannabis. In this study, the most common THC-induced ADRs were dry mouth and/or dry throat, tachycardia, nausea, and arrhythmia. Across the whole sample, we found that 52.31% of Thai patients carried a heterozygous variant (rs806365, CT allele). Moreover, the number of rs806365 (CC, homozygous variant) carriers totaled seventeen people (26.15%) amongst the subjects of Thai patients treated with medical cannabis. Furthermore, 17 out of 22 patients (77.27%) who experienced severe ADRs: Tachycardia and/or arrhythmia, carried an abnormal rs806365 gene (CT and CC alleles). Conclusions: The results propose that the rs806365 gene is widely distributed amongst the Thai population and there is a link between this gene and vulnerability to developing THC-induced ADRs after being treated with medical cannabis. Therefore, it is necessary to screen for the rs806365 gene before using medical cannabis to treat a patient.

Keywords: rs806365, THC-induced adverse drug reactions, CB1 receptor, Thai population

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Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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Authors: Shabana Noureen, Zafar Mahmood

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Economies consistently engage in trade across borders and face tariff, non-tariff barriers and other quotas that constitute trade costs. The trade costs imposed by policy barriers on exports are considered an impediment in the export growth rate. This work aims to measure over-year trends in total and bilateral trade costs and their trends in relevance to policy barriers (tariff and non-tariff). The analysis through the micro-founded theoretically based gravity model showed that the total trade costs have a general decreasing trend in the world while in the case of developing countries, the rate by which these trends decline is very low. Bilateral trade cost estimates associated with the policy barriers represent that the non-tariff barriers in a developing country have a major role in sustaining the high trade costs as compared to the tariff barriers. This ultimately leads to a low net declining rate. This work emphasizes that for developing countries the non-tariff barriers are a major factor that renders their exports and to be uncompetitive in the world market.

Keywords: trade costs, policy barriers, tariff barriers, non-tariff barriers, trade policies, export growth

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Authors: F. Husem, M. E. Turan, Y. Sun, H. Ahlatci, I. Tozlu

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Residual stress and fatigue crack growth rates are important to determine mechanical behavior of rails. This study aims to make relationship between residual stress and fatigue crack growth values in rails. For this purpose, three R260 quality rails (0.6-0.8% C, 0.6-1.25 Mn) were chosen. Residual stress of samples was measured by cutting method that is related in railway standard. Then samples were machined for fatigue crack growth test and analyze was completed according to the ASTM E647 standard which gives information about parameters of rails for this test. Microstructure characterizations were examined by Light Optic Microscope (LOM). The results showed that residual stress change with fatigue crack growth rate. The sample has highest residual stress exhibits highest crack growth rate and pearlitic structure can be seen clearly for all samples by microstructure analyze.

Keywords: residual stress, fatigue crack growth, R260, SEM, ASTM E647

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Authors: Cyril Hrncar, Jozef Bujko, Widya P. B. Putra

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The growth curve of poultry is important to evaluate the farming management system. This study was aimed to estimate the growth curve of body weight in goose. The growth curve in this study was estimated with non-linear Gompertz model through CurveExpert 1.4. software. Three Slovak mixed-sex goose breeds of Landes (L), Pomeranian (P) and Steinbacher (S) were used in this study. Total of 28 geese (10 L, 8 P and 10 S) were used to estimate the growth curve. Research showed that the asymptotic weight (A) in those geese were reached of 5332.51 g (L), 6186.14 g (P) and 5048.27 g (S). Thus, the maturing rate (k) in each breed were similar (0.05 g/day). The weight of inflection was reached of 1960.48 g (L), 2274.32 g (P) and 1855.98 g (S). The time of inflection (ti) was reached of 25.6 days (L), 26.2 days (P) and 27.80 days (S). The maximum growth rate (MGR) was reached of 98.02 g/day (L), 113.72 g/day (P) and 92.80 g/day (S). Hence, the coefficient of determination (R2) in Gompertz model was 0.99 for each breed. It can be concluded that Pomeranian geese had highest of growth trait than the other breeds.

Keywords: body weight, growth curve, inflection, Slovak geese, Gompertz model

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Authors: B. J. Mahen, N. E. Lloyd-Gale, S. Johnson, W. P. Rakowicz, M. J. Harris, A. D. Miller

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Background: Migraine is a leading cause of disability in the world. Calcitonin gene-related peptide (CGRP) receptor antagonists offer an approach to migraine prophylaxis by inhibiting the inflammatory and vasodilatory effects of CGRP. In recent years, NICE licensed the use of three CGRP-receptor antagonists: Fremanezumab, Galcanezumab, and Erenumab. Here, we present the outcomes of CGRP-antagonist treatment in a cohort of patients who suffer from episodic or chronic migraine and have failed at least three oral prophylactic therapies. Methods: We offered CGRP antagonists to 86 patients who met the NICE criteria to start therapy. We recorded the number of headache days per month (HDPM) at 0 weeks, 3 months, and 12 months. Of those, 26 patients were switched to an alternative treatment due to poor response or side effects. Of the 112 total cases, 9 cases did not sufficiently maintain their headache diary, and 5 cases were not followed up at 3 months. We have therefore included 98 sets of data in our analysis. Results: Fremanezumab achieved a reduction in HDPM by 51.7% at 3 months (p<0.0001), with 63.7% of patients meeting NICE criteria to continue therapy. Patients trialed on Galcanezumab attained a reduction in HDPM by 47.0% (p=0.0019), with 51.6% of patients meeting NICE criteria to continue therapy. Erenumab, however, only achieved a reduction in HDPM by 17.0% (p=0.29), and this was not statistically significant. Furthermore, 34.4%, 9.7%, and 4.9% of patients taking Fremanezumab, Galcanezumab, and Erenumab, respectively, continued therapy beyond 12 months. Of those who attempted drug holidays following 12 months of treatment, migraine symptoms relapsed in 100% of cases. Conclusion: We observed a significant improvement in HDPM amongst episodic and chronic migraine patients following treatment with Fremanezumab or Galcanezumab.

Keywords: migraine, CGRP, fremanezumab, galcanezumab, erenumab

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Authors: Sabrina Barsky, Ashley Monks

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In humans, exercise improves symptoms of various pathological states, although exercise adaptations seem to differ in response to sex. Skeletal muscle anabolism is thought to be regulated by androgen receptor (AR) through poorly specified mechanisms. Interactions of AR and exercise on muscle phenotype remain inconclusive in males, and undetermined in females. We hypothesized that sex differences in exercise adaptations are regulated by the androgenic system and the type of exercise performed. Here we examined interactions between a muscle-specific AR overexpression transgene (HSA-AR) and forced aerobic exercise paradigm on muscle and adipose exercise adaptation in male and female rats. We used dual-energy X-ray absorptiometry (DXA) to examine body composition adaptations post 9-week exercise protocol. We replicated the effects of HSA-AR on body composition, with males only having increased % lean mass and reduced % fat mass (P<0.05). Aerobic exercise improved lean body phenotype significantly, with lesser indices of total and % fat mass (P<0.01) in both sexes. Sex-specific effects of exercise included decreased total body mass (P<0.01) in males and increased lean mass % (P<0.001) in females. Surprisingly, neither AR manipulation nor exercise affected bone parameters in either sex. This varied response in total mass and lean mass according to exercise presents a sexually dimorphic response to exercise. Neither sex showed an interaction between HSA-AR and forced aerobic exercise on body composition. Future work is proposed to examine the effects of exercise type (aerobic versus resistance) and the role of gonadal androgens in sexually dimorphic exercise-mediated mitochondrial adaptations. This work implicates the development of sex-specific exercise therapies.

Keywords: androgen receptor, forced exercise, muscle physiology, sexual dimorphism

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Authors: Chayakarn Bamrungbutr, James Sillitoe

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The term ‘shadow port’ is used to describe a port whose markets are dominated by an adjacent port that has a more competitive capability. Recently, researchers have put effort into studying the mechanisms of how a regional port, in the shadow of a nearby predominant port which is a capital city port, can compete and grow. However, such mechanism is still unclear. This study thus focuses on understanding the growth of shadow port and the type of shadow port by using the two capital city ports of Thailand; Bangkok port (the former main port) and Laem Chabang port (the current main port), as the case study. By developing an understanding of the mechanisms of shadow, port could ultimately lead to an increase in the competitiveness. In this study, a framework of opportunity capture (introduced by Magala, 2004) will be used to create a framework for the study of the growth of the selected shadow port. In the process of building this framework, five groups of port development experts, consisting of government, council, academia, logistics provider and industry, will be interviewed. To facilitate this work, the Noticing, Collecting and Thinking model which was developed by Seidel (1998) will be used in an analysis of the dataset. The resulting analysis will be used to classify the type of shadow port. The type of these ports will be a significant factor for developing a feasible strategic guideline for the future management planning of ports, particularly, shadow ports, and then to increase the competitiveness of a nation’s maritime transport industry, and eventually lead to a boost in the national economy.

Keywords: shadow port, Bangkok Port, Laem Chabang Port, port growth

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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Authors: Reetika Sharma, Lalit Tejwani, Himanshu Shekhar, Arun Singhvi

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Purpose: To describe a novel technique of trabeculectomy targeting triple modulation on wound healing to increase the overall success rate. Method: Ten eyes of 10 patients underwent trabeculectomy with subconjunctival mitomycin C (0.4mg/ml for 4 minutes) application combined with Ologen implantation subconjunctivally and subsclerally. Five of these patients underwent additional phacoemulsification with intraocular lens implantation. The Ologen implant was wet with 0.1 ml Bevacizumab. Result: All the eyes achieved target intraocular pressure (IOP), which was maintained until one year of follow-up. Two patients needed anterior chamber reformation at day two post surgery. One patient needed cataract surgery after four months of surgery and achieved target intraocular pressure on two topical antiglaucoma medicines. Conclusion: Vascular endothelial growth factor (VEGF) concentration has been seen to increase in the aqueous humor after filtration surgery. Ologen implantation helps in collagen remodelling, antifibroblastic response, and acts as a spacer. Bevacizumab augmented Ologen, in addition, targets the increased VEGF and helps in decreasing scarring. Anti-VEGF augmented Ologen in trabeculectomy with mitomycin C (MMC) hence appears to have encouraging short-term intraocular pressure control.

Keywords: ologen, anti-VEGF, trabeculectomy, scarring

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Authors: Hummaira Qudsia Yousaf, Sidra Munawar

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The study aims to examine in which way entrepreneurial education and attitude affect the entrepreneur’s success with the help of an entrepreneurial mindset, professional growth, and innovation. The target population was the entrepreneurs of successful startups in Pakistan. Data was gathered through an e-questionnaire, and 230 responses were analyzed using the partial least square structural equation modeling (PLS-SEM). Resultantly, entrepreneurial education is an essential component for the development of an entrepreneurial mindset. Also, an entrepreneurial attitude is responsible for the entrepreneurial mindset, which enhances professional growth. Moreover, the study highlighted that innovation is as necessary as mindset and education are for entrepreneurs. Furthermore, the findings confirmed that professional growth brings innovation to the success of entrepreneurs. This study provides proof of how entrepreneurial education and attitude influence pupils’ success in making entrepreneurs. This study extends the scope of education by incorporating predictors, such as professional growth, innovation, and entrepreneurial success. The study is unique due to the usage of innovative techniques for professional growth that ultimately bring career success.

Keywords: entrepreneurial education, entrepreneurial attitude, entrepreneurial mindset, professional growth, entrepreneurial success, innovation

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Authors: Ihtisham Bukhari

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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.

Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome

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Authors: Elham Sharif, Nasser Rizk, Sirin Abu Aqel, Ofelia Masoud

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Background: Previous studies have investigated the association of rs1544410, rs7975232 and rs731236 polymorphisms in vitamin D receptor gene and its impact on diseases such as cancer, diabetes and hypertension in different ethnic backgrounds. Aim: The aim of this study is to investigate the association between VDR polymorphisms using three SNP’s (rs1544410, rs7975232 and rs731236) and the severity of the significant lesion in coronary arteries among angiographically diagnosed CAD. Methods: A prospective-retrospective study was conducted on 192 CAD patients enrolled from the cardiology department-Heart Hospital HMC, grouped in 96 subjects with significant stenosis and 96 with non-significant stenosis with a mean age between 30 and 75 years old. Genotyping was performed for the following SNPs rs1544410, rs7975232 and rs731236 using TaqMan assay by the Real Time PCR, ABI 7500 in Health Sciences Labs at Qatar University Biomedical Research Center. Results: The results showed that both groups have matched age and gender distribution but patients with the significant stenosis have significantly higher; BMI (p=0.047); smoking status (p=0.039); FBS (p= 0.031); CK-MB (p=0.025) and Troponin (p=0.002) than the patients with non–significant lesion. Among the traditional risk factors, smoking increases the odds of the severe stenotic lesion in CAD patients by 1.984, with 95% CI between 1.024 – 7.063, with p= 0.042.HWE showed deviations of the rs1544410 and rs731236 among the study subjects. The most frequent genotype in distribution of rs7975232 is the AA among the significant stenosis patients, while the heterozygous AC was the frequent genotype in distribution among the non-significant stenosis group. The carriers of CC genotype in rs7975232 increased the risk of having significant coronary arteries stenotic lesion by 1.83 with 95% CI (1.020 – 3.280), p=0.043. No association was found between the rs7975232 with vitamin D and VDBP. Conclusion: There is a significant association between rs7975232 and the severity of CAD lesion. The carrier of CC genotype in rs7975232 increased the risk of having significant coronary arteries atherosclerotic lesion especially in patients with smoking history independent of vitamin D.

Keywords: vitamin D, vitamin D receptor, polymorphism, coronary harat disease

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Authors: Lisnawati Hutagalung

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Background: Low birth weight (LBW) is one cause of newborn death. Babies with low birth weight tend to have slower cognitive development, growth retardation, more at risk of infectious disease event at risk of death. Objective: Identifying risk factors and dominant factors that influence the incidence of LBW in Indonesia. Method: This research used some database of public health such as Google Scholar, UGM journals, UI journals and UNAND journals in 2012-2015. Data were filtered using keywords ‘Risk Factors’ AND ‘Cause LBW’ with amounts 2757 study. The filtrate obtained 5 public health research that meets the criteria. Results: Risk factors associated with LBW, among other environment factors (exposure to cigarette smoke and residence), social demographics (age and socio-economic) and maternal factors (anemia, placental abnormal, nutritional status of mothers, examinations antenatal, preeclampsia, parity, and complications in pregnancy). Anemia and nutritional status become the dominant factor affecting LBW. Conclusions: The risk factors that affect LBW, most commonly found in the maternal factors. The dominant factors are a big effect on LBW is anemia and nutritional status of the mother during pregnancy.

Keywords: low birth weight, anemia, nutritional status, the dominant factor

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Authors: M. Pourshirazi, M. Esmaelifar, A. Aliahmadi, F. Yazdian, A. S. Hatamian Zarami, S. J. Ashrafi

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Monascus purpureus is an antioxidant-producing fungus whose secondary metabolites can be used in drug industries. The growth yield and antioxidant activity of extract were investigated in 3-L liquid fermentation media in a 5-L stirred tank bioreactor (STD) at 30°C, pH 5.93 and darkness for 4 days with 150 rpm agitation and 40% dissolved oxygen. Results were compared to extract isolated from Erlenmeyer flask with the same condition. The growth yield was 0.21 and 0.17 in STD condition and Erlenmeyer flask, respectively. Furthermore, the IC50 of DPPH scavenging activity was 256.32 µg/ml and 150.43 µg/ml for STD extract and flask extract, respectively. Our data demonstrated that transferring the growth condition into the STD caused an increase in growth yield but not in antioxidant activity. Accordingly, there is no relationship between growth rate and secondary metabolites formation. More studies are needed to determine the mass transfer coefficient and also evaluating the hydrodynamic condition have to be done in the future studies.

Keywords: Monascus purpureus, bioreactor, antioxidant, growth yield

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Authors: Loubna Safar, Lama Youssef, Majd Aljamali

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Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide. Complement factor H polymorphism (Y402H) is thought to play a potential role in the predisposition to AMD and response of patients with exudative AMD to treatment with anti-Vascular Endothelial Growth Factor (anti-VEGF). This study aimed to investigate the frequency of Y402H among Syrians, its impact on their susceptibility to AMD, and the hypothesized role of Y402H in patients' response to intravitreal anti-VEGF (i.e.,, bevacizumab). Our case-control study encompassed unrelated 54 AMD cases and 44 controls. Genotyping was determined by standard sequencing of PCR products. Frequency was compared between patients and controls, and correlation between genotype and response to treatment was assessed in 20 patients with wet AMD who received a therapeutic course of three intravitreal bevacizumab injections (once monthly). Our results revealed a significantly higher prevalence of the risk allele C among AMD cases (51.9%) in comparison with controls (37.5%) (P= 0.04, OR= 1.386, CI= 0.999- 1.923). Patients with the TT genotype (no risk allele) exhibited a significantly better primary response rate, reached 87.5% compared to only 41.7% in patients carrying the risk allele C (TC + CC), (P= 0.04, OR= 9.8, CI=0.899- 106.84). The findings of this study prove the importance of investigating Y402H polymorphism as a prognostic marker for predicting response to bevacizumab in AMD patients.

Keywords: age-related macular degeneration, bevacizumab, complement factor H gene, polymorphism, Y402H

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Authors: K. Farheen, A. Munir

Abstract:

Seismic response of the multi-storey buildings is created by the interaction of both the structure and underlying soil medium. The seismic design philosophy is incorporated using response modification factor 'R'. Current code based values of 'R' factor does not reflect the SSI problem as it is based on fixed base condition. In this study, the modified values of 'R' factor for moment resisting frame (MRF) considering SSI are evaluated. The response of structure with and without SSI has been compared using equivalent linear static and nonlinear static pushover analyses for 10-storied moment resisting frame building. The building is located in seismic zone 2B situated on different soils with shear wave velocity (Vₛ) of 300m/sec (SD) and 1200m/s (SB). Code based 'R' factor value for building frame system has been taken as 5.5. Soil medium is modelled using identical but mutually independent horizontal and vertical springs. It was found that the modified 'R' factor values have been decreased by 47% and 43% for soil SD and SB respectively as compared to that of code based 'R' factor.

Keywords: buildings, SSI, shear wave velocity, R factor

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