Search results for: Nima Khosravi
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 59

Search results for: Nima Khosravi

29 Prevalence of Overweight and Obesity in Iron-Deficient Iranian Teenagers Girls

Authors: Eftekhari M. H., Mozaffari-Khosravi H., Shidfar F.

Abstract:

Background: Many Iranian adolescent girls are iron deficient, but it is unclear whether the iron deficiency is associated with other nutritional risk indicators. Objective: we aimed to investigate the association between iron deficiency and weight status (measured as BMI) among a reprehensive sample of teenage girls. Methods: A cross-sectional study was performed in a region of southern I.R.Iran. One hundred eighty-seven iron-deficient participants (aged between 11 to 14) were selected by systematic random sampling among all students in grades 1 to 3 from high schools for girls. We assayed hemoglobin, hematocrit, serum ferritin, iron and total iron binding capacity and measured weight and height. Body mass index was calculated according to age and gender-specific BMI growth charts for children 2 to 20 years of age. Results: 13% were at risk for being overweight and 8.3% were overweight. The severity of iron deficiency increased as BMI increased from normal to at risk for overweight and overweight. Iron deficiency anemia was most prevalent among overweight adolescents than at risk for overweight and normal weight adolescents (28%, 18%, and 13%, respectively). Conclusions: The results of this study showed an inverse association of BMI with serum ferritin. Overweight adolescents demonstrated an increased prevalence of anemia. Because of the potentially harmful effects of iron deficiency, obese adolescents should be routinely screened and treated as necessary.

Keywords: adolescent, over weight, iron deficiency, Iran

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28 A Stochastic Analytic Hierarchy Process Based Weighting Model for Sustainability Measurement in an Organization

Authors: Faramarz Khosravi, Gokhan Izbirak

Abstract:

A weighted statistical stochastic based Analytical Hierarchy Process (AHP) model for modeling the potential barriers and enablers of sustainability for measuring and assessing the sustainability level is proposed. For context-dependent potential barriers and enablers, the proposed model takes the basis of the properties of the variables describing the sustainability functions and was developed into a realistic analytical model for the sustainable behavior of an organization. This thus serves as a means for measuring the sustainability of the organization. The main focus of this paper was the application of the AHP tool in a statistically-based model for measuring sustainability. Hence a strong weighted stochastic AHP based procedure was achieved. A case study scenario of a widely reported major Canadian electric utility was adopted to demonstrate the applicability of the developed model and comparatively examined its results with those of an equal-weighted model method. Variations in the sustainability of a company, as fluctuations, were figured out during the time. In the results obtained, sustainability index for successive years changed form 73.12%, 79.02%, 74.31%, 76.65%, 80.49%, 79.81%, 79.83% to more exact values 73.32%, 77.72%, 76.76%, 79.41%, 81.93%, 79.72%, and 80,45% according to priorities of factors that have found by expert views, respectively. By obtaining relatively necessary informative measurement indicators, the model can practically and effectively evaluate the sustainability extent of any organization and also to determine fluctuations in the organization over time.

Keywords: AHP, sustainability fluctuation, environmental indicators, performance measurement

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27 Comparison of Different Techniques to Estimate Surface Soil Moisture

Authors: S. Farid F. Mojtahedi, Ali Khosravi, Behnaz Naeimian, S. Adel A. Hosseini

Abstract:

Land subsidence is a gradual settling or sudden sinking of the land surface from changes that take place underground. There are different causes of land subsidence; most notably, ground-water overdraft and severe weather conditions. Subsidence of the land surface due to ground water overdraft is caused by an increase in the intergranular pressure in unconsolidated aquifers, which results in a loss of buoyancy of solid particles in the zone dewatered by the falling water table and accordingly compaction of the aquifer. On the other hand, exploitation of underground water may result in significant changes in degree of saturation of soil layers above the water table, increasing the effective stress in these layers, and considerable soil settlements. This study focuses on estimation of soil moisture at surface using different methods. Specifically, different methods for the estimation of moisture content at the soil surface, as an important term to solve Richard’s equation and estimate soil moisture profile are presented, and their results are discussed through comparison with field measurements obtained from Yanco1 station in south-eastern Australia. Surface soil moisture is not easy to measure at the spatial scale of a catchment. Due to the heterogeneity of soil type, land use, and topography, surface soil moisture may change considerably in space and time.

Keywords: artificial neural network, empirical method, remote sensing, surface soil moisture, unsaturated soil

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26 Changing Left Ventricular Hypertrophy After Kidney Transplantation

Authors: Zohreh Rostami, Arezoo Khosravi, Mohammad Nikpoor Aghdam, Mahmood Salesi

Abstract:

Background: Cardiovascular mortality in chronic kidney disease (CKD) and end stage renal disease (ESRD) patients have a strong relationship with baseline or progressive left ventricular hypertrophy (LVH) meanwhile in hemodialysis patients 10% decrement in left ventricular mass was associated with 28% reduction in cardiovascular mortality risk. In consonance with these arguments, we designed a study to measure morphological and functional echocardiographic variations early after transplantation. Method: The patients with normal renal function underwent two advanced echocardiographic studies to examine the structural and functional changes in left ventricular mass before and 3-month after transplantation. Results: From a total of 23 participants 21(91.3%) presented with left ventricular hypertrophy, 60.9% in eccentric and 30.4% in concentric group. Diastolic dysfunction improved in concentric group after transplantation. Both in pre and post transplantation global longitudinal strain (GLS)- average in eccentric group was more than concentric (-17.45 ± 2.75 vs -14.3 ± 3.38 p=0.03) and (-18.08 ± 2.6 vs -16.1 ± 2.7 p= 0.04) respectively. Conclusion: Improvement and recovery of left ventricular function in concentric group was better and sooner than eccentric after kidney transplantation. Although fractional shortening and diastolic function and GLS-4C in pre-transplantation in concentric group was worse than eccentric, but therapeutic response to kidney transplantation in concentric was more and earlier than eccentric group.

Keywords: chronic kidney disease, end stage renal disease, left ventricular hypertrophy, global longitudinal strain

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25 Application of the Electrical Resistivity Tomography and Tunnel Seismic Prediction 303 Methods for Detection Fracture Zones Ahead of Tunnel: A Case Study

Authors: Nima Dastanboo, Xiao-Qing Li, Hamed Gharibdoost

Abstract:

The purpose of this study is to investigate about the geological properties ahead of a tunnel face with using Electrical Resistivity Tomography ERT and Tunnel Seismic Prediction TSP303 methods. In deep tunnels with hydro-geological conditions, it is important to study the geological structures of the region before excavating tunnels. Otherwise, it would lead to unexpected accidents that impose serious damage to the project. For constructing Nosoud tunnel in west of Iran, the ERT and TSP303 methods are employed to predict the geological conditions dynamically during the excavation. In this paper, based on the engineering background of Nosoud tunnel, the important results of applying these methods are discussed. This work demonstrates seismic method and electrical tomography as two geophysical techniques that are able to detect a tunnel. The results of these two methods were being in agreement with each other but the results of TSP303 are more accurate and quality. In this case, the TSP 303 method was a useful tool for predicting unstable geological structures ahead of the tunnel face during excavation. Thus, using another geophysical method together with TSP303 could be helpful as a decision support in excavating, especially in complicated geological conditions.

Keywords: tunnel seismic prediction (TSP303), electrical resistivity tomography (ERT), seismic wave, velocity analysis, low-velocity zones

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24 Biosorption of Metal Ions from Sarcheshmeh Acid Mine Drainage by Immobilized Bacillus thuringiensis in a Fixed-Bed Column

Authors: V. Khosravi, F. D. Ardejani, A. Aryafar, M. Sedighi

Abstract:

Heavy metals have a damaging impact for the environment, animals and humans due to their extreme toxicity and removing them from wastewaters is a very important and interesting task in the field of water pollution control. Biosorption is a relatively new method for treatment of wastewaters and recovery of heavy metals. In this study, a continuous fixed bed study was carried out by using Bacillus thuringiensis as a biosorbent for the removal of Cu and Mn ions from Sarcheshmeh Acid Mine Drainage (AMD). The effect of operating parameters such as flow rate and bed height on the sorption characteristics of B. thuringiensis was investigated at pH 6.0 for each metal ion. The experimental results showed that the breakthrough time decreased with increasing flow rate and decreasing bed height. The data also indicated that the equilibrium uptake of both metals increased with decreasing flow rate and increasing bed height. BDST, Thomas, and Yoon–Nelson models were applied to experimental data to predict the breakthrough curves. All models were found suitable for describing the whole dynamic behavior of the column with respect to flow rate and bed height. In order to regenerate the adsorbent, an elution step was carried out with 1 M HCl and five adsorption-desorption cycles were carried out in continuous manner.

Keywords: acid mine drainage, bacillus thuringiensis, biosorption, cu and mn ions, fixed bed

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23 Wind Power Forecasting Using Echo State Networks Optimized by Big Bang-Big Crunch Algorithm

Authors: Amir Hossein Hejazi, Nima Amjady

Abstract:

In recent years, due to environmental issues traditional energy sources had been replaced by renewable ones. Wind energy as the fastest growing renewable energy shares a considerable percent of energy in power electricity markets. With this fast growth of wind energy worldwide, owners and operators of wind farms, transmission system operators, and energy traders need reliable and secure forecasts of wind energy production. In this paper, a new forecasting strategy is proposed for short-term wind power prediction based on Echo State Networks (ESN). The forecast engine utilizes state-of-the-art training process including dynamical reservoir with high capability to learn complex dynamics of wind power or wind vector signals. The study becomes more interesting by incorporating prediction of wind direction into forecast strategy. The Big Bang-Big Crunch (BB-BC) evolutionary optimization algorithm is adopted for adjusting free parameters of ESN-based forecaster. The proposed method is tested by real-world hourly data to show the efficiency of the forecasting engine for prediction of both wind vector and wind power output of aggregated wind power production.

Keywords: wind power forecasting, echo state network, big bang-big crunch, evolutionary optimization algorithm

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22 Hybrid Laser-Gas Metal Arc Welding of ASTM A106-B Steel Pipes

Authors: Masoud Mohammadpour, Nima Yazdian, Radovan Kovacevic

Abstract:

The Oil and Gas industries are vigorously looking for new ways to increase the efficiency of their pipeline constructions. Besides the other approaches, implementing of new welding methods for joining pipes can be the best candidate on this regard. Hybrid Laser Arc Welding (HLAW) with the capabilities of high welding speed, deep penetration, and excellent gap bridging ability can be a possible alternative method in pipeline girth welding. This paper investigates the feasibility of applying the HLAW to join ASTM A106-B as the mostly used piping material for transporting high-temperature and high-pressure fluids and gases. The experiments were carried out on six-inch diameter pipes with the wall thickness of 10mm. AWS ER 70 S6 filler wire with diameter of 1.2mm was employed. Relating to this welding procedure, characterization of welded samples such as hardness, tensile testing and Charpy V-notch testing were performed and the results will be reported in this paper. In order to have better understanding about the thermal history and the microstructural alterations caused by the welding heat cycle, a comprehensive Finite Element (FE) model was also conducted. The obtained results have shown that the Gas Metal Arc Welding (GMAW) procedure with the minimum number of 5 passes to complete the wall thickness, was reduced to only single pass by using the HLAW process with the welding time less than 15s.

Keywords: finite element modeling, high-temperature service, hybrid laser/arc welding, welding pipes

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21 MLProxy: SLA-Aware Reverse Proxy for Machine Learning Inference Serving on Serverless Computing Platforms

Authors: Nima Mahmoudi, Hamzeh Khazaei

Abstract:

Serving machine learning inference workloads on the cloud is still a challenging task at the production level. The optimal configuration of the inference workload to meet SLA requirements while optimizing the infrastructure costs is highly complicated due to the complex interaction between batch configuration, resource configurations, and variable arrival process. Serverless computing has emerged in recent years to automate most infrastructure management tasks. Workload batching has revealed the potential to improve the response time and cost-effectiveness of machine learning serving workloads. However, it has not yet been supported out of the box by serverless computing platforms. Our experiments have shown that for various machine learning workloads, batching can hugely improve the system’s efficiency by reducing the processing overhead per request. In this work, we present MLProxy, an adaptive reverse proxy to support efficient machine learning serving workloads on serverless computing systems. MLProxy supports adaptive batching to ensure SLA compliance while optimizing serverless costs. We performed rigorous experiments on Knative to demonstrate the effectiveness of MLProxy. We showed that MLProxy could reduce the cost of serverless deployment by up to 92% while reducing SLA violations by up to 99% that can be generalized across state-of-the-art model serving frameworks.

Keywords: serverless computing, machine learning, inference serving, Knative, google cloud run, optimization

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20 Chemometric Determination of the Geographical Origin of Milk Samples in Malaysia

Authors: Shima Behkami, Nor Shahirul Umirah Idris, Sharifuddin Md. Zain, Kah Hin Low, Mehrdad Gholami, Nima A. Behkami, Ahmad Firdaus Kamaruddin

Abstract:

In this work, Inductively Coupled Plasma Mass Spectrometry (ICP-MS), Isotopic Ratio Mass Spectrometry (IRMS) and Ultrasound Milko Tester were used to study milk samples obtained from various geographical locations in Malaysia. ICP-MS was used to determine the concentration of trace elements in milk, water and soil samples obtained from seven dairy farms at different geographical locations in peninsular Malaysia. IRMS was used to analyze the milk samples for isotopic ratios of δ13C, 15N and 18O. Nutritional parameters in the milk samples were determined using an ultrasound milko tester. Data obtained from these measurements were evaluated by Principal Component Analysis (PCA) and Hierarchical Analysis (HA) as a preliminary step in determining geographical origin of these milk samples. It is observed that the isotopic ratios and a number of the nutritional parameters are responsible for the discrimination of the samples. It was also observed that it is possible to determine the geographical origin of these milk samples solely by the isotopic ratios of δ13C, 15N and 18O. The accuracy of the geographical discrimination is demonstrated when several milk samples from a milk factory taken from one of the regions under study were appropriately assigned to the correct PCA cluster.

Keywords: inductively coupled plasma mass spectroscopy ICP-MS, isotope ratio mass spectroscopy IRMS, ultrasound, principal component analysis, hierarchical analysis, geographical origin, milk

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19 Probabilistic Models to Evaluate Seismic Liquefaction In Gravelly Soil Using Dynamic Penetration Test and Shear Wave Velocity

Authors: Nima Pirhadi, Shao Yong Bo, Xusheng Wan, Jianguo Lu, Jilei Hu

Abstract:

Although gravels and gravelly soils are assumed to be non-liquefiable because of high conductivity and small modulus; however, the occurrence of this phenomenon in some historical earthquakes, especially recently earthquakes during 2008 Wenchuan, Mw= 7.9, 2014 Cephalonia, Greece, Mw= 6.1 and 2016, Kaikoura, New Zealand, Mw = 7.8, has been promoted the essential consideration to evaluate risk assessment and hazard analysis of seismic gravelly soil liquefaction. Due to the limitation in sampling and laboratory testing of this type of soil, in situ tests and site exploration of case histories are the most accepted procedures. Of all in situ tests, dynamic penetration test (DPT), Which is well known as the Chinese dynamic penetration test, and shear wave velocity (Vs) test, have been demonstrated high performance to evaluate seismic gravelly soil liquefaction. However, the lack of a sufficient number of case histories provides an essential limitation for developing new models. This study at first investigates recent earthquakes that caused liquefaction in gravelly soils to collect new data. Then, it adds these data to the available literature’s dataset to extend them and finally develops new models to assess seismic gravelly soil liquefaction. To validate the presented models, their results are compared to extra available models. The results show the reasonable performance of the proposed models and the critical effect of gravel content (GC)% on the assessment.

Keywords: liquefaction, gravel, dynamic penetration test, shear wave velocity

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18 Combined Aerobic-Resistance Exercise Training and Broccoli Supplementation on Plasma Decitin-1 and Insulin Resistance in Men with Type 2 Diabetes

Authors: Mohammad Soltani, Ayoub Saeidi, Nikoo Khosravi, Hanieh Nohbaradar, Seyedeh Parya Barzanjeh, Hassane Zouhal

Abstract:

Exercise training and herbs supplement represent have role in the treatment for patients with type 2 diabetes (T2D). However, it is unclear combined effects of exercise training and herbs supplements on diabetic risk markers. This study aimed to determine the effect of 12 weeks of combined exercise and broccoli supplementation on decitin-1 and insulin resistance in men with type 2 diabetes. Forty-four type 2 diabetes men (age, 48.52 ± 4.36) were randomly allocated to training -supplement (TS, n = 11), training- placebo (TP, n = 11), supplement (S, n = 11) and control- placebo (CP, n = 11) groups. The combined exercise program included 12 weeks, three sessions per week, that each session contained 45 minutes of resistance training with intensity 60-70% of one maximal repetition and 30 minutes aerobic training (running) with intensity 60-70% of maximum heart rate. In addition supplement groups consumed 10 grams of Broccoli per day for 12 weeks. Plasma Decitin-1, HOMA-IR, Insulin, glucose and body composition were assessed before and after training. Plasma Dectin-1, HOMA-IR, glucose and BMI significantly decreased in TS, TP and S groups compared with CP group (P < .05). In addition Insulin and skeletal muscles mass showed significant increase in TS and TP groups compared with S and CP groups (P < .05). It is concluded that both combined exercise training (aerobic-resistance) or broccoli supplement can improve plasma Decitin-1 and insulin resistance in two diabetic patients however combine of exercise training and broccoli supplement have more effective on these markers.

Keywords: broccoli supplements, combined training, decitin-1, insulin resistance, type 2 diabetes

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17 Application of Analytic Hierarchy Process Model to Weight and Prioritize Challenges and Barriers to Strategic Approach

Authors: Mohammad Mehdi Mohebi, Nima Kazempour, Mohammad Naeim Kazempour

Abstract:

Strategic thinking enables managers to find out what factors are effective in achieving the desired goals and how these factors create value for the customer. Strategic thinking can be interpreted as a form of mental and inner strength in the manager, who by utilizing it, while considering the conditions of the environment and unstable global environment changes, takes decisions, and plans actions, and designs the strategy of his organization in today's changing and unsustainable business environment. Strategic thinking is very important in today’s business world, because without this thinking, the organization's efforts to achieve developed strategies will not be effective. In this study, through a detailed study of the challenges and barriers to strategic thinking that is carried out by various scholars and experts theoretically and experimentally, 7 major factors were identified. Then, based on these main factors of challenges and related elements, a tool in the form of a questionnaire was developed in order to determine their importance and priority from the perspective of strategic management experts. Using statistical tests the reliability and validity of this instrument, including its structural validity, has been examined and approved using factor analysis. These factors are weighted and prioritized using AHP techniques and the opinions of scholars and experts. Prioritization of barriers to strategic thinking include: lack of participatory management, lack of a systematic approach, difficulty in aligning the organization members, lack of incentive organizational culture, behavioural and internal barriers of managers, lack of key managers and lack of access to timely and accurate information.

Keywords: strategic thinking, challenges and barriers to strategic thinking, EN bank, AHP method

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16 Assessment and Evaluation Resilience of Urban Neighborhoods in Coping with Natural Disasters in in the Metropolis of Tabriz (Case Study: Region 6 of Tabriz)

Authors: Ali panahi-Kosar Khosravi

Abstract:

Earthquake resilience is one of the most important theoretical and practical concepts in crisis management. Over the past few decades, the rapid growth of urban areas and developing lower urban areas (especially in developing countries) have made them more vulnerable to human and natural crises. Therefore, the resilience of urban communities, especially low-income and unhealthy neighborhoods, is of particular importance. The present study seeks to assess and evaluate the resilience of neighborhoods in the center of district 6 of Tabriz in terms of awareness, knowledge and personal skills, social and psychological capital, managerial-institutional, and the ability to return to appropriate and sustainable conditions. The research method in this research is descriptive-analytical. The authors used library and survey methods to collect information and a questionnaire to assess resilience. The statistical population of this study is the total households living in the four neighborhoods of Shanb Ghazan, Khatib, Gharamalek, and Abuzar alley. Three hundred eighty-four families from four neighborhoods were selected based on the Cochran formula using a simple random sampling method. A one-sample t-test, simple linear regression, and structural equations were used to test the research hypotheses. Findings showed that only two social and psychological awareness and capital indicators in district 6 of Tabriz had a favorable and approved status. Therefore, considering the multidimensional concept of resilience, district 6 of Tabriz is in an unfavorable resilience situation. Also, the findings based on the analysis of variance indicated no significant difference between the neighborhoods of district 6 in terms of resilience, and most neighborhoods are in an unfavorable situation.

Keywords: resilience, statistical analysis, earthquake, district 6 of tabriz

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15 The First Report of Aberrant Corneal Occlusion in Rabbit in Iran

Authors: Bahador Bardshiri, Omid Moradi, Amir Komeilian, Nima Panahifar

Abstract:

Formation of a conjunctival membrane over the corneal surface is a condition unique to rabbits that has been labeled aberrant corneal occlusion or pseudopterygium. In the summer of 2013, a five years old male Standard Chinchilla rabbit were presented to Karaj Central Veterinary hospital and the owner complained that his rabbit shows degrees of blindness and there were opacities on both eyes of the presented rabbit. Ophthalmic examination of the affected eyes revealed a conjunctival fold stretching over the cornea of both eyes. The fold originated from limbus and it was vascularized and centrally thickened. There were no attachments to the corneal epithelium and the fold could be easily lifted. Surgery was performed under general anesthesia. The conjunctival fold was incised centrifugally up to its attachment at the limbus and the lid margin using small scissors. The central rim of the segment was then replaced to its normal position in the fornix and fixed with mattress sutures (7/0) passing through outside skin. After the surgery, eye drops containing dexamethasone, gentamicin and polymixin were applied twice daily up to 3 weeks. Within the observation period (8 months) no recurrence was noted. "Pseudo" in the term pseudopterygium refers to the fact that the conjunctival membrane is not adhering to the underlying cornea, but growing over it. In rare cases, the membrane may be loosely attached to the cornea, but can be easily separated without causing damage. It can cover only a small part of the cornea with an annular peripheral opacification of the cornea, or cover it almost fully, leading to blindness. Ethiopathogenesis remains unclear and recurrence of the problem is very likely. The surgical technique that used here decreases probability of recurrence of conjunctival fold.

Keywords: rabbit, cornea, aberrant corneal occlusion, pseudopterygium

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14 Factors That Influence Choice of Walking Mode in Work Trips: Case Study of Rasht, Iran

Authors: Nima Safaei, Arezoo Masoud, Babak Safaei

Abstract:

In recent years, there has been a growing emphasis on the role of urban planning in walking capability and the effects of individual and socioeconomic factors on the physical activity levels of city dwellers. Although considerable number of studies are conducted about walkability and for identifying the effective factors in walking mode choice in developed countries, to our best knowledge, literature lacks in the study of factors affecting choice of walking mode in developing countries. Due to the high importance of health aspects of human societies and in order to make insights and incentives for reducing traffic during rush hours, many researchers and policy makers in the field of transportation planning have devoted much attention to walkability studies; they have tried to improve the effective factors in the choice of walking mode in city neighborhoods. In this study, effective factors in walkability that have proven to have significant impact on the choice of walking mode, are studied at the same time in work trips. The data for the study is collected from the employees in their workplaces by well-instructed people using questionnaires; the statistical population of the study consists of 117 employed people who commute daily from work to home in Rasht city of Iran during the beginning of spring 2015. Results of the study which are found through the linear regression modeling, show that people who do not have freedom of choice for choosing their living locations and need to be present at their workplaces in certain hours have lower levels of walking. Additionally, unlike some of the previous studies which were conducted in developed countries, coincidental effects of Body Mass Index (BMI) and the income level of employees, do not have a significant effect on the walking level in work travels.

Keywords: BMI, linear regression, transportation, walking, work trips

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13 Adherence to Dietary Approaches to Stop Hypertension-Style Diet and Risk of Mortality from Cancer: A Systematic Review and Meta-Analysis of Cohort Studies

Authors: Roohallah Fallah-Moshkani, Mohammad Ali Mohsenpour, Reza Ghiasvand, Hossein Khosravi-Boroujeni, Seyed Mehdi Ahmadi, Paula Brauer, Amin Salehi-Abargouei

Abstract:

Purpose: Several investigations have proposed the protective association between dietary approaches to stop hypertension (DASH) style diet and risk of cancers; however, they have led to inconsistent results. The present study aimed to systematically review the prospective cohort studies conducted in this regard and, if possible, to quantify the overall effect of using meta-analysis. Methods: PubMed, EMBASE, Scopus, and Google Scholar were searched for cohort studies published up to December 2017. Relative risks (RRs) which were reported for fully adjusted models and their confidence intervals were extracted for meta-analysis. Random effects model was incorporated to combine the RRs. Results: Sixteen studies were eligible to be included in the systematic review from which 8 reports were conducted on the effect of DASH on the risk of mortality from all cancer types, four on the risk of colorectal cancer, and three on the risk of colon and rectal cancer. Four studies examined the association with other cancers (breast, hepatic, endometrial, and lung cancer). Meta-analysis showed that high concordance with DASH significantly decreases the risk of all cancer types (RR=0.83, 95% confidence interval (95%CI):0.80-0.85); furthermore participants who highly adhered to the DASH had lower risk of developing colorectal (RR=0.79, 95%CI: 0.75-0.83), colon (RR=0.81, 95%CI: 0.74-0.87) and rectal (RR=0.79, 95%CI: 0.63-0.98) cancer compared to those with the lowest adherence. Conclusions: DASH-style diet should be suggested as a healthy approach to protect from cancer in the community. Prospective studies exploring the effect on other cancer types and from regions other than the United States are highly recommended.

Keywords: cancer, DASH-style diet, dietary patterns, meta-analysis, systematic review

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12 Relationship of Epidermal Growth Factor Receptor Gene Mutations Andserum Levels of Ligands in Non-Small Cell Lung Carcinoma Patients

Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

Abstract:

Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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11 Application of Functionalized Magnetic Particles as Demulsifier for Oil‐in‐Water Emulsions

Authors: Hamideh Hamedi, Nima Rezaei, Sohrab Zendehboudi

Abstract:

Separating emulsified oil contaminations from waste- or produced water is of interest to various industries. Magnetic particles (MPs) application for separating dispersed and emulsified oil from wastewater is becoming more popular. Stabilization of MPs is required through developing a coating layer on their surfaces to prevent their agglomeration and enhance their dispersibility. In this research, we study the effects of coating material, size, and concentration of iron oxide MPs on oil separation efficiency, using oil adsorption capacity measurements. We functionalize both micro-and nanoparticles of Fe3O4 using sodium dodecyl sulfate (SDS) as an anionic surfactant, cetyltrimethylammonium bromide (CTAB) as a cationic surfactant, and stearic acid (SA). The chemical structures and morphologies of these particles are characterized using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Energy Dispersive X-ray (EDX). The oil-water separation results indicate that a low dosage of the coated magnetic nanoparticle with CTAB (0.5 g/L MNP-CTAB) results the highest oil adsorption capacity (nearly 100%) for 1000 ppm dodecane-in-water emulsion, containing ultra-small droplets (250–300 nm). While separation efficiency of the same dosage of bare MNPs is around 57.5%. Demulsification results of magnetic microparticles (MMPs) also reveal that the functionalizing particles with CTAB increase oil removal efficiency from 86.3% for bare MMP to 92% for MMP-CTAB. Comparing the results of different coating materials implies that the major interaction reaction is an electrostatic attraction between negatively charged oil droplets and positively charged MNP-CTAB and MMP-CTAB. Furthermore, the synthesized nanoparticles could be recycled and reused; after ten cycles the oil adsorption capacity slightly decreases to near 95%. In conclusion, functionalized magnetic particles with high oil separation efficiency could be used effectively in treatment of oily wastewater. Finally, optimization of the adsorption process is required by considering the effective system variables, and fluid properties.

Keywords: oily wastewater treatment, emulsions, oil-water separation, adsorption, magnetic nanoparticles

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10 Using 3-Glycidoxypropyltrimethoxysilane Functionalized Silica Nanoparticles to Improve Flexural Properties of E-Glass/Epoxy Grid-Stiffened Composite Panels

Authors: Reza Eslami-Farsani, Hamed Khosravi, Saba Fayazzadeh

Abstract:

Lightweight and efficient structures have the aim to enhance the efficiency of the components in various industries. Toward this end, composites are one of the most widely used materials because of durability, high strength and modulus, and low weight. One type of the advanced composites is grid-stiffened composite (GSC) structures which have been extensively considered in aerospace, automotive, and aircraft industries. They are one of the top candidates for replacing some of the traditional components which are used here. Although there are a good number of published surveys on the design aspects and fabrication of GSC structures, little systematic work has been reported on their material modification to improve their properties, to our knowledge. Matrix modification using nanoparticles is an effective method to enhance the flexural properties of the fibrous composites. In the present study, a silane coupling agent (3-glycidoxypropyltrimethoxysilane/3-GPTS) was introduced onto the silica (SiO2) nanoparticle surface and its effects on the three-point flexural response of isogrid E-glass/epoxy composites were assessed. Based on the fourier transform infrared spectrometer (FTIR) spectra, it was inferred that the 3-GPTS coupling agent was successfully grafted onto the surface of SiO2 nanoparticles after modification. Flexural test revealed an improvement of 16%, 14%, and 36% in stiffness, maximum load and energy absorption of the isogrid specimen filled with 3 wt.% 3-GPTS/SiO2 compared to the neat one. It would be worth mentioning that in these structures, a considerable energy absorption was observed after the primary failure related to the load peak. Also, 3-GPTMS functionalization had a positive effect on the flexural behavior of the multiscale isogrid composites. In conclusion, this study suggests that the addition of modified silica nanoparticles is a promising method to improve the flexural properties of the grid-stiffened fibrous composite structures.

Keywords: isogrid-stiffened composite panels, silica nanoparticles, surface modification, flexural properties, energy absorption

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9 Using 3-Glycidoxypropyltrimethoxysilane Functionalized SiO2 Nanoparticles to Improve Flexural Properties of Glass Fibers/Epoxy Grid-Stiffened Composite Panels

Authors: Reza Eslami-Farsani, Hamed Khosravi, Saba Fayazzadeh

Abstract:

Lightweight and efficient structures have the aim to enhance the efficiency of the components in various industries. Toward this end, composites are one of the most widely used materials because of durability, high strength and modulus, and low weight. One type of the advanced composites is grid-stiffened composite (GSC) structures, which have been extensively considered in aerospace, automotive, and aircraft industries. They are one of the top candidates for replacing some of the traditional components, which are used here. Although there are a good number of published surveys on the design aspects and fabrication of GSC structures, little systematic work has been reported on their material modification to improve their properties, to our knowledge. Matrix modification using nanoparticles is an effective method to enhance the flexural properties of the fibrous composites. In the present study, a silane-coupling agent (3-glycidoxypropyltrimethoxysilane/3-GPTS) was introduced onto the silica (SiO2) nanoparticle surface and its effects on the three-point flexural response of isogrid E-glass/epoxy composites were assessed. Based on the fourier transform infrared spectrometer (FTIR) spectra, it was inferred that the 3-GPTS coupling agent was successfully grafted onto the surface of SiO2 nanoparticles after modification. Flexural test revealed an improvement of 16%, 14%, and 36% in stiffness, maximum load and energy absorption of the isogrid specimen filled with 3 wt.% 3-GPTS/SiO2 compared to the neat one. It would be worth mentioning that in these structures, considerable energy absorption was observed after the primary failure related to the load peak. In addition, 3-GPTMS functionalization had a positive effect on the flexural behavior of the multiscale isogrid composites. In conclusion, this study suggests that the addition of modified silica nanoparticles is a promising method to improve the flexural properties of the grid-stiffened fibrous composite structures.

Keywords: isogrid-stiffened composite panels, silica nanoparticles, surface modification, flexural properties

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8 Urban Sustainable Development with Flood Crisis Management Approach

Authors: Ali Liaghat, Navid Tavanpour, Nima Tavanpour

Abstract:

An increase in population and prevalence of urbanity have led plan makers and decision makers put effort into sustainable development of cities at national and local levels. One of the important issues in urban development is compliance with safety issues in cities. Despite natural disasters and unexpected events such as floods, earthquakes, hurricanes, fires, etc., urban development should be regarded as an axiom, or else any form of construction and development is not safe, because it will greatly harm economic growth and development and pose an obstacle to achieving sustainable development, plus a loss to lives and finances of people. Therefore, in line with urban development, it is necessary to identify particular environmental and local issues as determinants and pay attention to them at the top of everything, in that we can call it a good action and factor in urban sustainable developments. Physical structure of each city represents how it has developed or its development shaped and what incidents, changes, natural disasters it has undergone over time. Since any form of development plan should be in accordance with the previous situations of cities, disregarding it, unfortunately, can escalate into uncontrolled urban development, non-resistant and unstable construction against earthquake or invasion of river areas, destruction of agricultural lands or vegetation, periodic floods over time. It has been viewed as serious threats to developing cities, and typically caused destruction of bed and other urban facilities as well as damages to lives and finances. In addition, uncontrolled development has caused cities to look ugly in terms of urban façade, and off and on such unplanned measures caused the country to face countless losses, and it not only vitiates expenses incurred, but it will also impose additional costs of reconstruction, i.e. it is unsustainable development. Thus, in this paper, in addition to a discussion about necessity for a profound attitude toward this subject and making long-term plans, programs for organizing river and its surrounding area, creating open and green urban spaces, retrofitting and flood preventing are presented for sustainable safety and development of cities along with a critique of successful countries.

Keywords: flood, sustainable development, urbanisation, urban management

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7 Application of Gamma Frailty Model in Survival of Liver Cirrhosis Patients

Authors: Elnaz Saeedi, Jamileh Abolaghasemi, Mohsen Nasiri Tousi, Saeedeh Khosravi

Abstract:

Goals and Objectives: A typical analysis of survival data involves the modeling of time-to-event data, such as the time till death. A frailty model is a random effect model for time-to-event data, where the random effect has a multiplicative influence on the baseline hazard function. This article aims to investigate the use of gamma frailty model with concomitant variable in order to individualize the prognostic factors that influence the liver cirrhosis patients’ survival times. Methods: During the one-year study period (May 2008-May 2009), data have been used from the recorded information of patients with liver cirrhosis who were scheduled for liver transplantation and were followed up for at least seven years in Imam Khomeini Hospital in Iran. In order to determine the effective factors for cirrhotic patients’ survival in the presence of latent variables, the gamma frailty distribution has been applied. In this article, it was considering the parametric model, such as Exponential and Weibull distributions for survival time. Data analysis is performed using R software, and the error level of 0.05 was considered for all tests. Results: 305 patients with liver cirrhosis including 180 (59%) men and 125 (41%) women were studied. The age average of patients was 39.8 years. At the end of the study, 82 (26%) patients died, among them 48 (58%) were men and 34 (42%) women. The main cause of liver cirrhosis was found hepatitis 'B' with 23%, followed by cryptogenic with 22.6% were identified as the second factor. Generally, 7-year’s survival was 28.44 months, for dead patients and for censoring was 19.33 and 31.79 months, respectively. Using multi-parametric survival models of progressive and regressive, Exponential and Weibull models with regard to the gamma frailty distribution were fitted to the cirrhosis data. In both models, factors including, age, bilirubin serum, albumin serum, and encephalopathy had a significant effect on survival time of cirrhotic patients. Conclusion: To investigate the effective factors for the time of patients’ death with liver cirrhosis in the presence of latent variables, gamma frailty model with parametric distributions seems desirable.

Keywords: frailty model, latent variables, liver cirrhosis, parametric distribution

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6 Study of Growth Behavior of Some Bacterial Fish Pathogens to Combined Selected Herbal Essential Oil

Authors: Ashkan Zargar, Ali Taheri Mirghaed, Zein Talal Barakat, Alireza Khosravi, Hamed Paknejad

Abstract:

With the increase of bacterial resistance to the chemical antibiotics, replacing it with ecofriendly herbal materials and with no adverse effects in the host body is very important. Therefore, in this study, the effect of combined essential oil (Thymus vulgaris-Origanum magorana and Ziziphora clinopodioides) on the growth behavior of Yersinia ruckeri, Aeromonas hydrophila and Lactococcus garvieae was evaluated. The compositions of the herbal essential oils used in this study were determined by gas chromatography-mass spectrometry (GC-MS) while, the investigating of antimicrobial effects was conducted by the agar-disc diffusion method, determination of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), and bacterial growth curves determination relied on optical density (OD) at 630 nm. The main compounds were thymol (40.60 %) and limonene (15.98 %) for Thymus vulgaris while carvacrol (57.86 %) and thymol (13.54 %) were the major compounds in Origanum magorana. As regards Ziziphora clinopodiodes, α-pinene (22.6 %) and carvacrol (21.1 %) represented the major constituents. Concerning Yersinia ruckeri, disc-diffusion results showed that t.O.z (50 % Origanum majorana) combined essential oil was presented the best inhibition zone (30.66 mm) but it was exhibited no significant differences with other tested commercial antibiotics except oxytetracycline (P <0/05). The inhibitory activity and the bactericidal effect of the t.O.z, unveiled by the MIC= 0.2 μL /mL and MBC= 1.6 μL /mL values, were clearly the best between all combined oils. The growth behaviour of Yersinia ruckeri was affected by this combined essential oil and changes in temperature and pH conditions affected herbal oil performance. As regard Aeromonas hydrophila, its results were so similar to Yersinia ruckeri results and t.O.z (50 % Origanum majorana) was the best between all combined oils (inhibition zone= 26 mm, MIC= 0.4 μL /mL and MBC= 3.2 μL /mL, combined essential oil was affected bacterial growth behavior). Also for Lactococcus garvieae, t.O.z (50 % Origanum majorana) was the best between all combined oils having the best inhibition zone= 20.66 mm, MIC= 0.8 μL /mL and MBC= 1.6 μL /mL and best effect on inhibiting bacterial growth. Combined herbal essential oils have a good and noticeable effect on the growth behavior of pathogenic bacteria in the laboratory, and by continuing research in the host, they may be a suitable alternative to control, prevent and treat diseases caused by these bacteria.

Keywords: bacterial pathogen, herbal medicine, growth behavior, fish

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5 Novel Nickel Complex Compound Reactivates the Apoptotic Network, Cell Cycle Arrest and Cytoskeletal Rearrangement in Human Colon and Breast Cancer Cells

Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi

Abstract:

Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.

Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer

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4 Multi-Criteria Decision Making Tool for Assessment of Biorefinery Strategies

Authors: Marzouk Benali, Jawad Jeaidi, Behrang Mansoornejad, Olumoye Ajao, Banafsheh Gilani, Nima Ghavidel Mehr

Abstract:

Canadian forest industry is seeking to identify and implement transformational strategies for enhanced financial performance through the emerging bioeconomy or more specifically through the concept of the biorefinery. For example, processing forest residues or surplus of biomass available on the mill sites for the production of biofuels, biochemicals and/or biomaterials is one of the attractive strategies along with traditional wood and paper products and cogenerated energy. There are many possible process-product biorefinery pathways, each associated with specific product portfolios with different levels of risk. Thus, it is not obvious which unique strategy forest industry should select and implement. Therefore, there is a need for analytical and design tools that enable evaluating biorefinery strategies based on a set of criteria considering a perspective of sustainability over the short and long terms, while selecting the existing core products as well as selecting the new product portfolio. In addition, it is critical to assess the manufacturing flexibility to internalize the risk from market price volatility of each targeted bio-based product in the product portfolio, prior to invest heavily in any biorefinery strategy. The proposed paper will focus on introducing a systematic methodology for designing integrated biorefineries using process systems engineering tools as well as a multi-criteria decision making framework to put forward the most effective biorefinery strategies that fulfill the needs of the forest industry. Topics to be covered will include market analysis, techno-economic assessment, cost accounting, energy integration analysis, life cycle assessment and supply chain analysis. This will be followed by describing the vision as well as the key features and functionalities of the I-BIOREF software platform, developed by CanmetENERGY of Natural Resources Canada. Two industrial case studies will be presented to support the robustness and flexibility of I-BIOREF software platform: i) An integrated Canadian Kraft pulp mill with lignin recovery process (namely, LignoBoost™); ii) A standalone biorefinery based on ethanol-organosolv process.

Keywords: biorefinery strategies, bioproducts, co-production, multi-criteria decision making, tool

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3 Gender Specific Differences in Clinical Outcomes of Knee Osteoarthritis Treated with Micro-Fragmented Adipose Tissue

Authors: Tiffanie-Marie Borg, Yasmin Zeinolabediny, Nima Heidari, Ali Noorani, Mark Slevin, Angel Cullen, Stefano Olgiati, Alberto Zerbi, Alessandro Danovi, Adrian Wilson

Abstract:

Knee Osteoarthritis (OA) is a critical cause of disability globally. In recent years, there has been growing interest in non-invasive treatments, such as intra-articular injection of micro-fragmented fat (MFAT), showing great potential in treating OA. Mesenchymal stem cells (MSCs), originating from pericytes of micro-vessels in MFAT, can differentiate into mesenchymal lineage cells such as cartilage, osteocytes, adipocytes, and osteoblasts. Secretion of growth factor and cytokines from MSCs have the capability to inhibit T cell growth, reduced pain and inflammation, and create a micro-environment that through paracrine signaling, can promote joint repair and cartilage regeneration. Here we have shown, for the first time, data supporting the hypothesis that women respond better in terms of improvements in pain and function to MFAT injection compared to men. Historically, women have been underrepresented in studies, and studies with both sexes regularly fail to analyse the results by sex. To mitigate this bias and quantify it, we describe a technique using reproducible statistical analysis and replicable results with Open Access statistical software R to calculate the magnitude of this difference. Genetic, hormonal, environmental, and age factors play a role in our observed difference between the sexes. This observational, intention-to-treat study included the complete sample of 456 patients who agreed to be scored for pain (visual analogue scale (VAS)) and function (Oxford knee score (OKS)) at baseline regardless of subsequent changes to adherence or status during follow-up. We report that a significantly larger number of women responded to treatment than men: [90% vs. 60% change in VAS scores with 87% vs. 65% change in OKS scores, respectively]. Women overall had a stronger positive response to treatment with reduced pain and improved mobility and function. Pre-injection, our cohort of women were in more pain with worse joint function which is quite common to see in orthopaedics. However, during the 2-year follow-up, they consistently maintained a lower incidence of discomfort with superior joint function. This data clearly identifies a clear need for further studies to identify the cell and molecular biological and other basis for these differences and be able to utilize this information for stratification in order to improve outcome for both women and men.

Keywords: gender differences, micro-fragmented adipose tissue, knee osteoarthritis, stem cells

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2 Effect of Silica Nanoparticles on Three-Point Flexural Properties of Isogrid E-Glass Fiber/Epoxy Composite Structures

Authors: Hamed Khosravi, Reza Eslami-Farsani

Abstract:

Increased interest in lightweight and efficient structural components has created the need for selecting materials with improved mechanical properties. To do so, composite materials are being widely used in many applications, due to durability, high strength and modulus, and low weight. Among the various composite structures, grid-stiffened structures are extensively considered in various aerospace and aircraft applications, because of higher specific strength and stiffness, higher impact resistance, superior load-bearing capacity, easy to repair, and excellent energy absorption capability. Although there are a good number of publications on the design aspects and fabrication of grid structures, little systematic work has been reported on their material modification to improve their properties, to our knowledge. Therefore, the aim of this research is to study the reinforcing effect of silica nanoparticles on the flexural properties of epoxy/E-glass isogrid panels under three-point bending test. Samples containing 0, 1, 3, and 5 wt.% of the silica nanoparticles, with 44 and 48 vol.% of the glass fibers in the ribs and skin components respectively, were fabricated by using a manual filament winding method. Ultrasonic and mechanical routes were employed to disperse the nanoparticles within the epoxy resin. To fabricate the ribs, the unidirectional fiber rovings were impregnated with the matrix mixture (epoxy + nanoparticles) and then laid up into the grooves of a silicone mold layer-by-layer. At once, four plies of woven fabrics, after impregnating into the same matrix mixture, were layered on the top of the ribs to produce the skin part. In order to conduct the ultimate curing and to achieve the maximum strength, the samples were tested after 7 days of holding at room temperature. According to load-displacement graphs, the bellow trend was observed for all of the samples when loaded from the skin side; following an initial linear region and reaching a load peak, the curve was abruptly dropped and then showed a typical absorbed energy region. It would be worth mentioning that in these structures, a considerable energy absorption was observed after the primary failure related to the load peak. The results showed that the flexural properties of the nanocomposite samples were always higher than those of the nanoparticle-free sample. The maximum enhancement in flexural maximum load and energy absorption was found to be for the incorporation of 3 wt.% of the nanoparticles. Furthermore, the flexural stiffness was continually increased by increasing the silica loading. In conclusion, this study suggested that the addition of nanoparticles is a promising method to improve the flexural properties of grid-stiffened fibrous composite structures.

Keywords: grid-stiffened composite structures, nanocomposite, three point flexural test , energy absorption

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1 Pharmacological Mechanisms of an Indolic Compound in Chemoprevention of Colonic Acf Formation in Azoxymethane-Induced Colon Cancer Rat Model and Cell Lines

Authors: Nima Samie, Sekaran Muniandy, Zahurin Mohamed, M. S. Kanthimathi

Abstract:

Although number of indole containing compounds have been reported to have anticancer properties in vitro but only a few of them show potential as anticancer compounds in vivo. The current study was to evaluate the mechanism of cytotoxicity of selected indolic compound in vivo and in vitro. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, human monocyte/macrophage CRL-9855, and B lymphocyte CCL-156 cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content, measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results displayed a potent suppressive effect on HT-29 and WiDr after 24 h of treatment with IC50 value of 2.52±0.34 µg/ml and 2.13±0.65 µg/ml respectively. This cytotoxic effect on normal, monocyte/macrophage and B-cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the compound. Activation of this pathway was further evidenced by significant activation of caspase-9 and 3/7. The compound was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. These findings were further investigated for inhibitory efficiency of the compound on colonic aberrant crypt foci in male rats. Rats were divided in to 5 groups: vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of compounds for 10 weeks. Administration of compound suppressed total colonic ACF formation up to 73.4%. The results also showed that treatment with the compound significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. The outcome of this study suggest sthat the indolic compound is a potent anti-cancer agent against colon cancer and can be further evaluated by animal trial.

Keywords: indolic compound, chemoprevention, crypt, azoxymethane, colon cancer

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