Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 19

Search results for: Basamat S. Shaheen

19 Real-Space Mapping of Surface Trap States in Cigse Nanocrystals Using 4D Electron Microscopy

Authors: Riya Bose, Ashok Bera, Manas R. Parida, Anirudhha Adhikari, Basamat S. Shaheen, Erkki Alarousu, Jingya Sun, Tom Wu, Osman M. Bakr, Omar F. Mohammed

Abstract:

This work reports visualization of charge carrier dynamics on the surface of copper indium gallium selenide (CIGSe) nanocrystals in real space and time using four-dimensional scanning ultrafast electron microscopy (4D S-UEM) and correlates it with the optoelectronic properties of the nanocrystals. The surface of the nanocrystals plays a key role in controlling their applicability for light emitting and light harvesting purposes. Typically for quaternary systems like CIGSe, which have many desirable attributes to be used for optoelectronic applications, relative abundance of surface trap states acting as non-radiative recombination centre for charge carriers remains as a major bottleneck preventing further advancements and commercial exploitation of these nanocrystals devices. Though ultrafast spectroscopic techniques allow determining the presence of picosecond carrier trapping channels, because of relative larger penetration depth of the laser beam, only information mainly from the bulk of the nanocrystals is obtained. Selective mapping of such ultrafast dynamical processes on the surfaces of nanocrystals remains as a key challenge, so far out of reach of purely optical probing time-resolved laser techniques. In S-UEM, the optical pulse generated from a femtosecond (fs) laser system is used to generate electron packets from the tip of the scanning electron microscope, instead of the continuous electron beam used in the conventional setup. This pulse is synchronized with another optical excitation pulse that initiates carrier dynamics in the sample. The principle of S-UEM is to detect the secondary electrons (SEs) generated in the sample, which is emitted from the first few nanometers of the top surface. Constructed at different time delays between the optical and electron pulses, these SE images give direct and precise information about the carrier dynamics on the surface of the material of interest. In this work, we report selective mapping of surface dynamics in real space and time of CIGSe nanocrystals applying 4D S-UEM. We show that the trap states can be considerably passivated by ZnS shelling of the nanocrystals, and the carrier dynamics can be significantly slowed down. We also compared and discussed the S-UEM kinetics with the carrier dynamics obtained from conventional ultrafast time-resolved techniques. Additionally, a direct effect of the state trap removal can be observed in the enhanced photoresponse of the nanocrystals after shelling. Direct observation of surface dynamics will not only provide a profound understanding of the photo-physical mechanisms on nanocrystals’ surfaces but also enable to unlock their full potential for light emitting and harvesting applications.

Keywords: Optoelectronics, Surface Passivation, Nanocrystals, charge carrier dynamics, trap states

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18 Khaya Cellulose Supported Copper Nanoparticles for Chemo Selective Aza-Michael Reactions

Authors: Mashitah Mohd Yusoff, M. Shaheen Sarkar, M. Lutfor Rahman

Abstract:

We prepared a highly active Khaya cellulose supported poly(hydroxamic acid) copper nanoparticles by the surface modification of Khaya cellulose through graft co-polymerization and subsequently amidoximation. The Cu-nanoparticle (0.05 mol% to 50 mol ppm) was selectively promoted Aza-Michael reaction of aliphatic amines to give the corresponding alkylated products at room temperature in methanol. The supported nanoparticle was easy to recover and reused seven times without significance loss of its activity.

Keywords: Nanoparticles, Copper, Cellulose, Aza-Michael, poly(hydroxamic acid)

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17 Tourism Industry in Pakistan: Challenges Faced and Future Prospects

Authors: Misbah Shaheen, Anam Qureshi

Abstract:

In this work we will discuss the challenges faced by tourism industry in Pakistan. Tourism plays vital role in the socio-economic growth of a country. The countries of world, with less tourism opportunities are lagging behind from other nations of the world. Pakistan is one of those countries which rich in historical places, natural beauty, and uniqueness in handmade items and also of green forests. Present study will discuss the challenges being faced by tourism industry with special focus on hotel industry and law and order situation.

Keywords: Tourism, Pakistan, Hotel Industry, handmade items

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16 Dissatisfaction as a Cause of Social Uprisings: An Empirical Analysis Utilizing the Social Uprisings Composite Indicator

Authors: Sondos Shaheen

Abstract:

This paper employs a newly constructed composite indicator of social uprisings (SUCI) to analyze the causes of their occurrence. This empirical study is based on an unbalanced panel of 45 countries over the period of 1982–2007. The paper’s contribution to the literature is distinguishing between the causes of violent and nonviolent uprisings. The analysis shows that that certain variables have a significant impact on both violent and nonviolent uprisings in terms of relative SUCI values, for example, ethnic fractionalization and mountainous terrain. Nevertheless, differences between the causes of violent and nonviolent uprisings can be found. For example, life dissatisfaction is related to nonviolent social uprisings, but when life dissatisfaction is accompanied by democratic dissatisfaction, violent social uprisings are more likely.

Keywords: mobilization, causes, social uprisings, relative deprivation, dissatisfaction, anti-government movements

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15 Nuclear Decay Data Evaluation for 217Po

Authors: S. S. Nafee, S. A. Shaheen, A. M. Al-Ramady

Abstract:

Evaluated nuclear decay data for the 217Po nuclide ispresented in the present work. These data include recommended values for the half-life T1/2, α-, β--, and γ-ray emission energies and probabilities. Decay data from 221Rn α and 217Bi β—decays are presented. Q(α) has been updated based on the recent published work of the Atomic Mass Evaluation AME2012. In addition, the logft values were calculated using the Logft program from the ENSDF evaluation package. Moreover, the total internal conversion electrons has been calculated using Bricc program. Meanwhile, recommendation values or the multi-polarities have been assigned based on recently measurement yield a better intensity balance at the 254 keV and 264 keV gamma transitions.

Keywords: nuclear decay data evaluation, mass evaluation, total converison coefficients, atomic mass evaluation

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14 Financial Instruments of Islamic Banking: A Critical Analysis

Authors: Rukhsana Shaheen and Tahira Ifraq

Abstract:

Interest based transactions led the advent of Islamic banking. In order to provide an alternative to Interest based banking, financial transactions found in classical books of fiqh were employed. Musharakah, Mudarabah, Murabahah Salam, Ijara, and some other modes were adopted. These modes were modified so that they can be adopted for banking and satisfy the needs of customers. Since the inception of Islamic banking, these modes are being used and with the passage of time, are being molded and experimented with to cater different kinds of customers and requirements. Human efforts cannot be errorless. These modes too bear legal defects which need an in-depth scrutiny and refinement. The aim of this paper is to dig the basis and rulings of these modes in classical books of fiqh and analyze its modification and adoption in Islamic banking and the legal defects that these modes are bearing. Paper will prove itself fruitful by providing remedies for the legal defects.

Keywords: Islamic Banking, financial instruments, legal defects, remedies

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13 Multi-Criteria Decision Support System for Modeling of Civic Facilities Using GIS Applications: A Case Study of F-11, Islamabad

Authors: Khalid Mahmood, Asma Shaheen Hashmi, Omer Riaz, Fahad Ullah, Tanveer Ahmad

Abstract:

The urban landscapes are being change with the population growth and advancements in new technologies. The urban sprawl pattern and utilizes are related to the local socioeconomic and physical condition. Urban policy decisions are executed mostly through spatial planning. A decision support system (DSS) is very powerful tool which provides flexible knowledge base method for urban planning. An application was developed using geographical information system (GIS) for urban planning. A scenario based DSS was developed to integrate the hierarchical muti-criteria data of different aspects of urban landscape. These were physical environment, the dumping site, spatial distribution of road network, gas and water supply lines, and urban watershed management, selection criteria for new residential, recreational, commercial and industrial sites. The model provided a framework to incorporate the sustainable future development. The data can be entered dynamically by planners according to the appropriate criteria for the management of urban landscapes.

Keywords: Urban, Spatial, GIS, criteria

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12 Critical Discourse Analysis of Political TV Talk Show of Pakistani Media

Authors: Sumaira Saleem, Sajjad Hussain, Asma Kashif Shahzad, Hina Shaheen

Abstract:

This study aims at exploring the relationship between language and ideology and how such relationships are represented in the analysis of spoken texts, following Van Dijk’s Socio Cognitive Model (2002). In this study, it is tried to show that political Talk shows broadcast by Private TV channels are working apparatuses of ideology and store meanings which are not always obvious for readers. This analysis was about the situation created by Arslan Iftkhar, the son of ex-Chief Justice of Pakistan, Iftikhar Muhammad Chaudry and PTI Chief Imran Khan. Arslan Iftikhar submitted an application against Imran Khan that he is not able to become a member of parliament of Pakistan. In the application, he demanded the documents, which are submitted by Imran Khan at the time of Election to the Election Commission of Pakistan. Murad Ali from PTI also submitted an application against PM Nawaz Sharif to the Election Commission of Pakistan for providing the copies. It also suggests that these talk shows mystify the agency of processes by using various strategies. In other words, critical text analyses reveal how these choices enable speakers to manipulate the realizations of agency and power in the representation of action to produce particular meanings which are not always explicit for all readers.

Keywords: Power, Ideology, ECP, CDA, socio cognitive model, TV channels

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11 Parental Perceptions and Practices toward Childhood Asthma

Authors: Amani K. Abu-Shaheen, Abdullah Nofal, Humariya Heena

Abstract:

Introduction: Parental perceptions and practices are important for improving the asthma outcomes in children; indeed, evidence shows that parents of asthmatic children harbor considerable misperceptions of the disease. Objective: To identify the prevalence of asthma and to investigate the perceptions and practices of parents toward asthma and its management in Saudi children. Methods: A two-stage cross-sectional survey of 2000 parents of children aged 3–15 years from schools located in all five districts of Riyadh province located in central Saudi Arabia, was conducted. Data collection was accomplished using a self-administered questionnaire based on information obtained from the literature. Results: Of 1450 children whose parents participated in the study, 600 had asthma, dyspnea, or chest allergy. The overall number of children with parental reports of ever having been diagnosed with asthma was 478 (32.9%). The majority of parents (321, 53.5%) believed that asthma was a hereditary disease. Of these parents, 361 (60.3%) were concerned about side effects of inhaled steroids, and 192 (32%) about development of dependency on asthma medications. Three hundred sixty seven (61.2%) parents reported that they could treat the asthma attack at home and almost 76% of parents went to pediatric emergency department during asthma attack. Conclusions: In this study, the overall prevalence of children whose parents reported that they were diagnosed with asthma was high (32.9%). Furthermore, parents of children with asthma had misperceptions regarding asthma and exhibited ineffective practices in its management. To improve asthma care and compliance, adequate education should be provided to parents.

Keywords: Management, Asthma, Quality of Life, Parents

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10 Estimating Air Particulate Matter 10 Using Satellite Data and Analyzing Its Annual Temporal Pattern over Gaza Strip, Palestine

Authors: ِAbdallah A. A. Shaheen

Abstract:

Gaza Strip faces economic and political issues such as conflict, siege and urbanization; all these have led to an increase in the air pollution over Gaza Strip. In this study, Particulate matter 10 (PM10) concentration over Gaza Strip has been estimated by Landsat Thematic Mapper (TM) and Landsat Enhanced Thematic Mapper Plus (ETM+) data, based on a multispectral algorithm. Simultaneously, in-situ measurements for the corresponding particulate are acquired for selected time period. Landsat and ground data for eleven years are used to develop the algorithm while four years data (2002, 2006, 2010 and 2014) have been used to validate the results of algorithm. The developed algorithm gives highest regression, R coefficient value i.e. 0.86; RMSE value as 9.71 µg/m³; P values as 0. Average validation of algorithm show that calculated PM10 strongly correlates with measured PM10, indicating high efficiency of algorithm for the mapping of PM10 concentration during the years 2000 to 2014. Overall results show increase in minimum, maximum and average yearly PM10 concentrations, also presents similar trend over urban area. The rate of urbanization has been evaluated by supervised classification of the Landsat image. Urban sprawl from year 2000 to 2014 results in a high concentration of PM10 in the study area.

Keywords: Urbanization, landsat, PM10, atmospheric reflectance, Gaza strip

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9 Simulation of Laser Structuring by Three Dimensional Heat Transfer Model

Authors: Bassim Shaheen Bachy, Jörg Franke

Abstract:

In this study, a three dimensional numerical heat transfer model has been used to simulate the laser structuring of polymer substrate material in the Three-Dimensional Molded Interconnect Device (3D MID) which is used in the advanced multi-functional applications. A finite element method (FEM) transient thermal analysis is performed using APDL (ANSYS Parametric Design Language) provided by ANSYS. In this model, the effect of surface heat source was modeled with Gaussian distribution, also the effect of the mixed boundary conditions which consist of convection and radiation heat transfers have been considered in this analysis. The model provides a full description of the temperature distribution, as well as calculates the depth and the width of the groove upon material removal at different set of laser parameters such as laser power and laser speed. This study also includes the experimental procedure to study the effect of laser parameters on the depth and width of the removal groove metal as verification to the modeled results. Good agreement between the experimental and the model results is achieved for a wide range of laser powers. It is found that the quality of the laser structure process is affected by the laser scan speed and laser power. For a high laser structured quality, it is suggested to use laser with high speed and moderate to high laser power.

Keywords: Simulation, Finite Element Analysis, Thermal Modeling, Laser Structuring

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8 Clarification of Taxonomic Confusions among Adulterated Drugs Coffee Seena and Seena Weed through Systematic and Pharmaceutical Markers

Authors: Shabnum Shaheen, Farah Khan, Nida Haroon, Sumera Javad, Mehreen Jalal, Samina Sarwar

Abstract:

Coffee Senna is pharmaceutically very important and used for multiple health disorders such as gastric pains, indigestion, snakebites, asthma and fever, tuberculosis and menstrual problems. However, its immense medicinal value and great demand lead to adulteration issue which could be injurious for users. Some times its adulterant Seena weed (Senna occidentalis L.) is used as its substitute which definitely not as effective as Coffee Senna. Hence, the present study was undertaken to provide some tools for systematic and pharmaceutical authentication of a shrubby plant Coffee Senna (Cassia occidentalis Linn.). These parameters included macro and micro morphological characters, anatomical and palynomorph characterization, solubility, fluorescence and phytochemical analysis. By the application of these parameters acquired results revealed that, these two plants are distinct from each other. The Coffee Seena was found to be an annual shrub with trilobed pollen, diacytic, paracytic and anisocytic stomata whereas the Seena weed stands out as an annual or perennial herb with spheroidal and circular pollen and paracytic type of stomata. The powdered drug of Coffee seena is dark grayish green whereas the powdered drug of Seena weed is light green in color. These findings are constructive in authentic identification of these plants.

Keywords: coffee senna, Senna weed, taxonomic evaluation, pharmaceutical markers

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7 Hepatoprotective Activity of Sharbat Deenar, against Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Authors: Ashik Mosaddik, Nazmul Huda, Abdul Awal, Shafiqur Rahman, Rukhsana Shaheen, Mustofa Nabi

Abstract:

Polyherbal formulation Sharbat Deenar is a very popular unani medicine in Bangladesh. It is usually used for different kinds of liver disorders. In absence of reliable and inadequate hepatoprotective agents in conventional medicine, the herbal preparations are preferred for liver diseases. The present study was designed to evaluate the hepatoprotective activity of Sharbat Deenar on carbon tetrachloride (CCl4) induced hepatotoxicity in male Long-Evans albino rats. Group I served as normal control and received neither formulation nor carbon tetrachloride. Group II received only CCl4 1mL/kg body weight of rat intraperitoneally for consecutive 14 days. Group III received CCl4 1mL/kg body weight of rat intraperitoneally and Silymarin, in dose 50mg/kg body weight of rat orally. Group IV received CCl4 1mL/kg body weight of rat intraperitoneally and Sharbat Deenar 1mL/kg body weight of rat for the same 14 consecutive days. At the end of the study, hepatoprotective activity was evaluated by the levels of total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Histopathological study of rat liver was also carried out. The results showed that polyherbal formulation Sharbat Deenar exhibited a significant hepatoprotective effect. Such an outcome seems to be the synergistic effect of all ingredients of tested herbal formulation. Although this study suggests that Sharbat Deenar may be used to cure or minimize various liver diseases, it needs further study to attain the clarity of mechanism and safety.

Keywords: Silymarin, hepatoprotective, carbon tetrachloride, polyherbal formulation, sharbat deenar

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6 Geostatistical Simulation of Carcinogenic Industrial Effluent on the Irrigated Soil and Groundwater, District Sheikhupura, Pakistan

Authors: Javed Iqbal, Asma Shaheen

Abstract:

The water resources are depleting due to an intrusion of industrial pollution. There are clusters of industries including leather tanning, textiles, batteries, and chemical causing contamination. These industries use bulk quantity of water and discharge it with toxic effluents. The penetration of heavy metals through irrigation from industrial effluent has toxic effect on soil and groundwater. There was strong positive significant correlation between all the heavy metals in three media of industrial effluent, soil and groundwater (P < 0.001). The metal to the metal association was supported by dendrograms using cluster analysis. The geospatial variability was assessed by using geographically weighted regression (GWR) and pollution model to identify the simulation of carcinogenic elements in soil and groundwater. The principal component analysis identified the metals source, 48.8% variation in factor 1 have significant loading for sodium (Na), calcium (Ca), magnesium (Mg), iron (Fe), chromium (Cr), nickel (Ni), lead (Pb) and zinc (Zn) of tannery effluent-based process. In soil and groundwater, the metals have significant loading in factor 1 representing more than half of the total variation with 51.3 % and 53.6 % respectively which showed that pollutants in soil and water were driven by industrial effluent. The cumulative eigen values for the three media were also found to be greater than 1 representing significant clustering of related heavy metals. The results showed that heavy metals from industrial processes are seeping up toxic trace metals in the soil and groundwater. The poisonous pollutants from heavy metals turned the fresh resources of groundwater into unusable water. The availability of fresh water for irrigation and domestic use is being alarming.

Keywords: Groundwater, Heavy Metals, industrial effluent, geostatistical

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5 Levansucrase from Zymomonas Mobilis KIBGE-IB14: Production Optimization and Characterization for High Enzyme Yield

Authors: Shah Ali Ul Qader, Sidra Shaheen, Nadir Naveed Siddiqui

Abstract:

In recent years, significant progress has been made in discovering and developing new bacterial polysaccharides producing organisms possessing extremely functional properties. Levan is a natural biopolymer of fructose which is produced by transfructosylation reaction in the presence of levansucrase. It is one of the industrially promising enzymes that offer a variety of industrial applications in the field of cosmetics, foods and pharmaceuticals. Although levan has significant applications but the yield of levan produced is not equal to other biopolymers due to the inefficiency of producer microorganism. Among wide range of levansucrase producing microorganisms, Zymomonas mobilis is considered as a potential candidate for large scale production of this natural polysaccharide. The present investigation is concerned with the isolation of levansucrase producing natural isolate having maximum enzyme production. Furthermore, production parameters were optimized to get higher enzyme yield. Levansucrase was partially purified and characterized to study its applicability on industrial scale. The results of this study revealed that the bacterial strain Z. mobilis KIBGE-IB14 was the best producer of levansucrase. Bacterial growth and enzyme production was greatly influenced by physical and chemical parameters. Maximum levansucrase production was achieved after 24 hours of fermentation at 30°C using modified medium of pH-6.5. Contrary to other levansucrases, the one presented in the current study is able to produce high amount of products in relatively short period of time with optimum temperature at 35°C. Due to these advantages, this enzyme can be used on large scale for commercial production of levan and other important metabolites.

Keywords: Metabolites, Polysaccharides, levansucrase, transfructosylation

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4 Anti-Aging Effects of Retinol and Alpha Hydroxy Acid on Elastin Fibers of Artificially Photo-Aged Human Dermal Fibroblast Cell Lines

Authors: Mohammed Jarrar, Shalini Behl, Nadia Shaheen, Abeer Fatima, Reem Nasab

Abstract:

Skin aging is a slow multifactorial process influenced by both internal as well as external factors. Ultra-violet radiations (UV), diet, smoking and personal habits are the most common environmental factors that affect skin aging. Fat contents and fibrous proteins as collagen and elastin are core internal structural components. The direct influence of UV on elastin integrity and health is crucial on aging of skin by time. The deposition of abnormal elastic material is a major marker in a photo-aged skin. Searching for compounds that may protect against cutaneous photo-damage is highly valued. Retinoids and Alpha Hydroxy Acids protective and or repairing effects of UV have been endorsed by some researchers. For consolidating a better understanding of anti and protective effects of such anti-aging agents, we evaluated the combinatory effects of various dosages of lactic acid and retinol on the dermal fibroblasts elastin levels exposed to UV. The UV exposed cells showed significant reduction in the elastin levels. A combination of drugs with a higher concentration of lactic acid (30-35 mM) and a lower concentration of retinol (10-15mg/mL) showed to work better in enhancing elastin concentration in UV exposed cells. We assume this enhancement could be the result of increased tropo-elastin gene expression stimulated by retinol and lactic acid probably repaired the UV irradiated damage by enhancing the amount and integrity of the elastin fibers.

Keywords: alpha hydroxy acid, elastin, retinol, ultraviolet radiations

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3 Serosurveillance of Measles Virus amongst Vaccinated Children of a Rural Population of Sindh

Authors: Zeb Hussain, Muhammad Asif Qureshi, Shaheen Sharafat

Abstract:

Background: Measles is a contagious viral infection common in childhood. Vaccination against measles is included in the expanded program of immunization (EPI). However, and alarmingly, a high mortality rate is observed due to measles infection in Pakistan. Moreover a recent outbreak of measles in various areas of Pakistan further highlights the problem. It is therefore important to investigate measles specific IgG (antibody) levels in our population. Objective: To quantify measles specific IgG antibodies amongst vaccinated children in district Qamber Shahdadkot, Sindh. Methodology: This cross-sectional study was conducted at the Microbiology section of the Dow-Diagnostic-Research-and-Reference-Laboratory (DDRRL), DUHS after Institutional Review Board approval (IRB-516/DUHS/-14) during August-December-2014. A total of 173 participants (residents of district Qamber Shahdadkot, Sindh) aged between 1-5 years were recruited in the study. Blood samples were collected as per standard phlebotomy guidelines. Blood was stored at 4 °C overnight. Samples were subsequently spun at a speed of 10000rpm to separate sera, which were divided into small aliquots to be frozen at -20 °C. Frozen sera were transported to the DDRRL on dry ice. Measles specific IgG (antibody) titers were quantified using enzyme linked immunosorbant assay (ELISA). Results: Blood was collected from a total of 173 individuals ranging between 1-5 years of age. Of these, a total of 88 participants were males and 85 were females. Of the 173 investigated samples, only 53 (30.6%) showed protective IgG titers against measles while 120 (69%) were sero-negative. Measles specific IgG antibodies titers were higher in female participants compared to the males. Conclusion: Our data demonstrate that a substantial percentage of vaccinated children in district Qamber-Shahdadkot did not have protective antibody titres against measles. It is therefore extremely important to investigate measles specific IgG levels in various parts of Pakistan in order to implement appropriate protective measures.

Keywords: Pakistan, measles, sero-surveillance, vaccinated children

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2 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients

Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

Abstract:

Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: Diabetes, Pakistan, Polymorphism, T2DM, SLC47A1

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1 Qualitative Modeling of Transforming Growth Factor Beta-Associated Biological Regulatory Network: Insight into Renal Fibrosis

Authors: Jamil Ahmad, Ayesha Waqar Khan, Mariam Altaf, Shaheen Shahzad

Abstract:

Kidney fibrosis is an anticipated outcome of possibly all types of progressive chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) signaling pathway is responsible for production of matrix-producing fibroblasts and myofibroblasts in diseased kidney. In this study, a discrete model of TGF-beta (transforming growth factor) and CTGF (connective tissue growth factor) was constructed using Rene Thomas formalism to investigate renal fibrosis turn over. The kinetic logic proposed by Rene Thomas is a renowned approach for modeling of Biological Regulatory Networks (BRNs). This modeling approach uses a set of constraints which represents the dynamics of the BRN thus analyzing the pathway and predicting critical trajectories that lead to a normal or diseased state. The molecular connection between TGF-beta, Smad 2/3 (transcription factor) phosphorylation and CTGF is modeled using GenoTech. The order of BRN is CTGF, TGF-B, and SMAD3 respectively. The predicted cycle depicts activation of TGF-B (TGF-β) via cleavage of its own pro-domain (0,1,0) and presentation to TGFR-II receptor phosphorylating SMAD3 (Smad2/3) in the state (0,1,1). Later TGF-B is turned off (0,0,1) thereby activating SMAD3 that further stimulates the expression of CTGF in the state (1,0,1) and itself turns off in (1,0,0). Elevated CTGF expression reactivates TGF-B (1,1,0) and the cycle continues. The predicted model has generated one cycle and two steady states. Cyclic behavior in this study represents the diseased state in which all three proteins contribute to renal fibrosis. The proposed model is in accordance with the experimental findings of the existing diseased state. Extended cycle results in enhanced CTGF expression through Smad2/3 and Smad4 translocation in the nucleus. The results suggest that the system converges towards organ fibrogenesis if CTGF remains constructively active along with Smad2/3 and Smad 4 that plays an important role in kidney fibrosis. Therefore, modeling regulatory pathways of kidney fibrosis will escort to the progress of therapeutic tools and real-world useful applications such as predictive and preventive medicine.

Keywords: System Biology, Qualitative Modeling, CTGF, renal fibrosis signaling pathway

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