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This study aimed to provide a model for improving the quality of women's and girls' leisure time in the family with an approach based on physical activity in Isfahan province. This research was carried out using a qualitative method with a systematic approach of grounded theory. The theoretical population consisted of knowledgeable and experienced women's sports and leisure professors who also used the snowball method for sampling. The data collection tool and method were semi-structured individual interviews, and the interviews continued until the theoretical saturation of 15 interviews. For data analysis, a systematic approach includes three main steps: open coding, axial coding and selective coding. In the axial coding stage, the connection between the following categories of causal conditions (support of important others, organizing, applicability of activities, institutionalization of activities); context factors (environmental attractions, environmental conditions, sports attractions(; interfering factors (evolutionary changes, cultural and social barriers, gender hegemony, macro trends, structural barriers); strategies (education and culture building, measures to support women's recreational sports, promotion and development of physical activities, respect for the dignity of women and girls, justice in the implementation of activities, media support) and consequences of qualifying women's leisure time (reducing behavioral disorders, individual empowerment, collective empowerment, increasing participation) in terms of coding paradigm in Sports manufacturing corporations was determined; also in selective coding phases, each component of coding paradigm described. The province's sports managers can use the signs, concepts and categories identified in their plans to improve the leisure time of women and girls in the family with an approach based on physical activity and use the proposed appropriate strategies to compensate for the backwardness and development of women's sports.

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Purpose: The antigen binding fragments of camelids heavy chain antibodies are comprised in one single domain (VHH). The crystal structure of an isolated VHH indicated that it is a problate particle of 2.5 nm in diameter and ∼ 4 nm high, and has been referred to as a nanobody. The very close similarity of these molecules to human VHs illustrates the potential application of these novel products as an immunodiagnostic immunotherapeutic reagent. One of the key components in production, characterization and application of nanobodies in detection is the anti-nanobodiy HRP conjugate. Materials and Methods: Here, we report high expression and purification of some nanobodies against tumor markers. The nanobodies genes were sub-cloned into a pSJF9 vector to over-express the protein coupled with fusion tags in E. coli TG1. The expressed nanobodies were purified by immobilized metal affinity chromatography (IMAC). Described here is the preparation, purification and characterization of anti-nanobody antibody HRP conjugate for use in the various nanobody detection systems. Results: Analysis by SDS-PAGE and Western blotting demonstrated the integrity of the purified nanobodies. Because of application of several biochemical modifications, the produced anti-nanobodies HRP conjugate have efficient sensitivity and specificity. Conclusion: By setting the temperature, time and inducer reagent the nanobodies were produced in optimum yield. We concluded that the HRP conjugated anti-nanobody can detect nanobodies in various detection procedures with great sensitivity and accuracy.

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Objective: The greatest challenge in cancer gene therapy is to achieve the high specificity and efficiency in targeting of cancer cells. Because the goal of cancer gene therapy is to eradicate cancer cells, many therapeutic genes could be detrimental if unintentionally expressed in normal cells. Using promoter of the genes which are expressed specifically in cancer cells or have much more expression in cancer cells than normal cells, is very noticeable tool in cancer gene therapy (CGT). In this study we were searching for cancer specific promoter which could highly express therapeutic gene. Materials and methods: In order to apply a cancer specific promoter for creating a CGT construct, a promoter which have 34% similarity to Survivin core promoter was amplified from human genome by using Nested-PCR. Survivin is a member of anti-apoptotic gene and its over-expression was observed in up to 70% of breast cancers. This gene fragment contains two transcriptional binding sites which were similar to Survivin promoter according to the evaluation of Promoter Scan, EPD, Transfac, Compel and TRRD program. These binding sites were recognized by STAT1 and E2F transcription factors. This promoter was cloned into pCDNA3.1/Hygro+ plasmid in along with hypoxia and estrogen modules and pro-apoptotic gene tBid. Results: Semi-quantitative RT-PCR results of transfected cancer cells showed that this gene fragment (Survivin like promoter) have relatively same potential as CMV promoter to direct tBid gene expression. Conclusion: Utilization of chimeric promoter containing Survivin like promoter could be a promising tool in killing cancer cells naturally by inducing apoptosis. This construct is highly effective in transcriptional targeting of tBid in comparison to control construct.

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Objective: Today, AIDS is considered as a global problem and many efforts to generate an effective vaccine against this disease have been made, but remain inconclusive. DNA vaccines are a member of the new generation of vaccines that can efficiently stimulate the immune system. However, recent findings indicate low immunogenicity for these vaccines and it is believed that these types of vaccines require strategies that could infer more immunogenicity. The employment of adjuvants could be considered as one of the most important methods involved. In this study, a DNA vaccine candidate for HIV P24-Nef is constructed and then using genetic adjuvants IL-15 and GM-CSF, cellular immune responses have been studied. Materials and Methods: In this study the gene structure of HIV P24-Nef in eukaryotic expression vector was constructed and expression vectors of IL-15 and GM-CSF were used as adjuvants. After inoculation of the candidate vaccine to BALB/c mice, cytokine patterns, lymphocytes proliferation and cytotoxicity were analyzed. Results: Our findings indicate that candidate vaccine significantly stimulated cellular immune responses. The usage of IL-15 and GM-CSF as DNA adjuvants together and separately with candidate vaccine has strengthened cellular immune responses significantly. Co-administration of DNA adjuvants significantly increased cellular immune responses when the ratio of the vaccine dose was more than the adjuvants. Conclusion: The sequences that we selected as candidate vaccine demonstrated good immunogenicity in mouse model and co-administration of IL-15 and GM-CSF DNA adjuvants increased cellular immune response to DNA vaccine construct.

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Objective: Several vaccines against HIV have been investigated but none has been approved as an effective HIV vaccine. An approach that could induce stronger immune response against the pathogen is utilizing a multi-epitopic vaccine. This strategy was used in the design of several vaccines and resulted in improved immune responses. Materials and Methods: In this study a multi-epitopic fusion peptide including parts of HIV-1 Nef and P24 as a vaccine candidate was injected into mice and immune humoral responses measured with total antibody and IgG sub-classes using ELISA. Also measurement of cellular immune responses through evaluation of spleen cells proliferation response using MTT and cytotoxicity by LDH were performed. Finally, the cytokine pattern of IFN-γ and IL-4 were also determined with ELISA. Results: The results indicate that candidate vaccine stimulated mouse splenic lymphocyte proliferation response and also induced strong cytotoxicity responses. Analysis of humoral immune response has shown that the candidate vaccine has induced specific antibody production mainly of the IgG2a sub-class. Also cytokine pattern evaluation has shown that IFN-γ secretion was dominant. Conclusion: The use of immunogen and conserved epitopes from P24 and Nef induced strong humoral and cellular immune responses and this construct could be candidate for further studies in animal models.

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Immunotoxins are an attractive way to treat cancer; in this method, high-cytotoxic protein toxins target cancer cells specifically. An immunotoxin consists of a targeting component (an antibody, cytokine, or other protein that binds to the cell), that is chemically conjugated or fused in DNA level to a cytotoxic cargo (a bacterium, plant or cytotoxic human protein). Immunotoxin, with the help of specific receptors, recognizes the target cell and enters the cell by endocytosis. After entering the cytocell, it kills the target cancer cell with the help of a toxic component. Although various immunotoxins with different structures have been studied and tested in recent decades, only three immunotoxins Denileukin Diftitox, Tagraxofusp and Moxestumomab Pasudotox - have been clinically approved for the treatment of leukemia. In this article, we review important research and two challenges in production and development of immunotoxins that have limited their clinical success. Further, we highlight methods to overcome these obstacles. These challenges include target and non-target cell toxicity and immunization.

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Objective: The objective of this study is to develop and assess targeted PAMAM-PEG nanocarrier with anti-TAG72 nanobody for t-Bid gene coding construct delivery into the human colonic adenocarcinoma cells. Materials and Methods: Nanobody (Nb) coding sequence was subcloned into pSJ expression vector for large-scale production and then Nb was purified by Ni++ affinity chromatography. SDS-PAGE and western blot analysis were performed to verify purifiction. PAMAM was reacted with PEG at the ratio 1:2 (mol/mol) and anti-TAG72 Nb at the ratio 1:1 (mol/mol). Surface charge and size of resulting nanoparticles were evaluated by Malvern zeta sizer and Nanosight. Efficiency of constructed gene carrier for t-Bid, a killer gene, delivery into colonic adenocarcinoma cells in in vitro was assessed using real time PCR and cell counting assays. Results: Production of nanoparticles with the average size of 162±92 nm and +4.57±0.52 zeta potential was confirmed by nanosight and Malvern zeta sizer in order. Gel retardation assay result verified efficiency of carrier for pDNA comlexation. Real time PCR results confirmed the target gene overexpression in the cancerous cell lines. Conclusion: The results of this research confirms the efficiency of PAMAM dendrimers for gene transferring, positive effect of PEGylation and targeting of nanoparticles by anti-TAG72 nanobody.

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Non-Newtonian fluid flows experience turbulent regime in some industrial applications. Several approaches have been proposed for numerical simulation of turbulent flows that each one has specific features. RANS turbulence models have reasonable computational costs, while include several sources of uncertainties affecting simulation results. In addition, developed RANS models for non-Newtonian fluids are modified versions of available models for Newtonian fluids, therefore, they cannot provide reliable estimation for viscoplastic stress term. On the contrary, DNS delivers accurate results but with high computational costs. Consequently, use of DNS data for estimation of uncertainty in RANS models can provide better decision making for engineers based on RANS results. In the present study, a turbulence model based on for power-law non-Newtonian fluid is developed and employed for simulation of flow in a pipe. Then, an efficient method is proposed for quantification of available model-form uncertainty. Moreover, it is assumed that uncertainties originating from various sources are combined together in calculation of Reynolds stress as well as viscoplastic stress. Deviation of the stresses, computed using RANS turbulence model, from DNS data are modeled through Gaussian Random Field. Thereafter, Karhunen-Loeve expansion is employed for uncertainty propagation in simulation process. Finally, the effects of these uncertainties on RANS results are shown in velocity field demonstrating the fact that the presented approach is accurate enough for statistical modeling of model-form uncertainty in RANS turbulence models.

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      Non-competition agreement as a protective tool for certain legitimate interests has special aspects, which have not been attended and analyzed in Iranian law. This paper, regarding the particular rules of American and European countries in this framework, provides a brief notion of the ongoing non-competition agreement is going to bring up detailed issues on its dissolution and clarify the principles on modification of non-competition agreement. The arguments and results of this article not only challenge the inflexible and traditional rules of Iranian law on this subject and make clear the necessity of revising in them, but also provide some patterns and solutions in confront of dissolving and adjusting of non-competition agreement for law.              
  *  Corresponding Author 's Email: Rahbarionlaw@gmail.com  

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In this study, a Lattice Boltzmann Method (LBM) has been developed to calculate the distribution of a scalar quantity, like temperature, in a natural convection flow field under the condition of varying fluid thermal conductivity. The standard form of an LBM usually considers the fluid properties to be constant without any source term in conservation equations. The model developed is to account for variation of thermal conductivity with temperature in the presence of an external heat source. The proposed model has been examined against various case studies. It is shown that it is capable of modeling the extremely nonlinear problems. To magnify the nonlinear term in the natural convection case of under study, the radiation and other thermal sources have been used. The multiple relaxation time scheme has been applied to assure the solution stability. Using Chapman-Enskog analysis, the error associated with the proposed model has been estimated. The part of error which was not due to variations in the fluid properties, may be eliminated by introducing a correction term in higher order terms in Chapman-Enskog analysis. In addition, it has been shown that the correction term associated with the fluid conductivity variations, create an error of second order in terms of Knudsen number and is negligible. The present LBM model has an error of the second order of magnitude with respect to time.

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Objective: Generation 5 poly (amidoamine) dendrimers are promising multipotent gene delivery vectors that provide favorable DNA condensation properties; however, their high toxicity limits their applications. Toxicity of PAMAM dendrimers depends on their type, generation and applied dosage in a way that lower generations (lower than G5 dendrimers) and anionic dendrimers have lower toxicity than higher generations and cationic dendrimers. The aim of this study is to evaluate the effect of PEGylation on toxicity of G5 PAMAM dendrimers. Methods: In this study, to improve their characteristics as gene delivery carriers, G5 PAMAM dendrimers were conjugated to polyethylene glycol molecules (PEG, molecular weight 3500) at three different molar ratios of 10, 20 and 30. Also the number of conjugated PEG chains was quantified using TNBSA and Ellman assays. The effect of different degrees of PEGylation on cytotoxicity and transfection efficiency of modified PAMAM dendrimers toward BT-474 and MCF-10A cell lines were assessed. Results: Compared to unconjugated, PEG conjugated PAMAM dendrimers had lower in vitro cytotoxicity, particularly at higher PEG to PAMAM molar ratios. Among all prepared PEG-PAMAM dendrimers, G5 PAMAM dendrimers that conjugated to PEG at a molar ratio of 10/1 had the highest in vitro transfection rate in both cell lines. Conclusion: Our results showed that these PEG-conjugated PAMAM dendrimers possess a great potential for in vitro gene delivery.

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Objective: Prostate cancer is the second cause of cancer-associated death in men. In recent years, targeted therapy for cancer has attracted the attention of researchers. Targeted therapy leads to a decrease in drug adverse effects. Studies indicate that targeting peptides for cancer cells represent valuable tools for diagnostics and therapeutics. Recently, phage display peptide libraries have been used to identify target peptides to a variety of cancer cells. In the current study, we aim to isolate peptides that target PC3 cells (human prostate adenocarcinoma cells). Methods: Four rounds of subtractive panning on control cells that included 5637 (bladder), Huh-7 (liver), SW480 (colon), AGS (stomach) and human fibroblast normal in addition to four rounds of positive panning on PC3 (target cell) were performed. Polyclonal phage ELISA was used to evaluate the process of enrichment during biopanning. Subsequently, phage clones were randomly selected from titer plates, amplified by plaque-PCR, and their genomic DNA was sequenced. We conducted bioinformatic analysis for further characterization of the isolated peptides. Results: Several rounds of panning resulted in the enrichment of a number of peptides. The results of polyclonal phage ELISA indicated that the biopanning process was successful. In silico analysis showed the presence of several consensus amino acid motifs in the peptides. Conclusion: The peptides identified through biopanning can be considered as potential specific binders to PC3 cells. Peptides with specificity binding to target cells can be used for targeted gene and drug delivery to malignant tumor cells. Further analyses of these peptides are required to show their capacity for targeted delivery of various genes and drugs into prostate cancer cells.

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Commitment decision as a new and efficient tool has recently assisted competition authorities in dealing with competitive concerns quickly, conveniently and crucially. Unfortunately, Iranian competition law has ignored such suitable enforcement. Accordingly, having regarded the notion and functional advantages of commitment decision, the present research, in comparative study of legal approaches of EU, US and some other eminent countries, is going to provide the most suitable and favored solutions about the procedure and formalities of making commitment decision and its content, the possibility and conditions of reviewing and appealing such decisions and sanctions imposed in non-compliance, which consistent with our particular competition framework, give rise to best results.  

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Concrete is the most widely used building material in construction industry worldwide and its constituents are easily accessible everywhere. However, cement industry, as the producer of the primary binder of concrete, is one of the effective sources of environment degradation. Cement production needs extraction of mineral resources and burning fuel and causes extensive greenhouse emission due to disintegration of raw materials. Cement production alone is responsible for 7% of global CO₂ emission with estimated annual growth of 4%. Toward environmental sustainability, one way is partially or totally replacing cement by waste or byproducts of other industries such as fly ash, ground granulated blast-furnace slag (GGBS), waste water, metakaolin, and silica fume. Geopolymer is a cementitious material with comparable characteristics to those of ordinary cement produced by alumina- and silica-rich waste materials. Therefore, it does not require energy-intensive and pollutive calcination process. Geopolymerization is formed by reaction of silica-alumina under an alkaline solution which creates three dimensional Si-O-Al-O polymeric chains to attain compressive strength, compared to the ordinary cement which develops calcium silicate hydrates (C-S-H) as the main adhesive. Extensive research has conducted on geopolymer concrete. However, more investigations are needed to better understand characteristics of geopolymer concrete containing additives. Fibers are proved to have a positive effect on mechanical strength of concrete. As well, fillers such as microsilica can improve mechanical and durability of concrete. Moreover, most studies in this area are focused on fly ash-based geopolymers and the investigations on GGBS-based geopolymer are rare in the literature. In this study, mechanical and durability of GGBS-based geopolymer concrete containing CFRP fibers and microsilica is investigated. Different concrete samples with 0-3% CFRP fibers and 0-10% microsilica are prepared and experimentally tested. Sodium Hydroxide (NH) and Sodium Silicate (NS) solutions are used as alkali activators. 8 M NH as well as NS with 14.7 Na₂O and 29.4 SiO₂are used with the NS/NH ratio of 2.5. Since no standard exists for mix design of geopolymer concrete, proposed mix design by Venkatesan and Pazhani (2015) is used. Alkaline to binder ratio of 0.4 is selected with 430 kg/m³binder.The specimens were tested after 28 days of curing. Next, mechanical and durability tests including compressive strength, tensile strength, ultrasonic pulse velocity, water absorption, RCPT, and acid resistance are conducted on the samples. Also, microstructure of the geopolymer concrete is investigated. Results of experimental tests show that, compressive and tensile strength of geopolymer samples decrease by adding microsilica. However, 5% microsilica is the best value to enhance mechanical properties of geopolymer concrete. On the other hand, microsilica can enhance durability properties of geopolymer concrete so that adding 5% microsilica causes moderate improvement of water absorption and chloride penetration. The greatest impact of microsilica is on acid resistance by which adding 5% microsilica resulted in 67% improvement of compressive strength loss. However, unlike the microsilica, CFRP fibers have detrimental effect on mechanical properties and durability of the geopolymer concrete since adding fibers can yield disruption of concrete integrity .On the other point of view, microstructure study shows that all the specimens exhibit micro cracks that can inversely affect the performance of concrete. Also, SEM images show that there is not a strong bond between CFRP fibers and binder paste which yields lower performance of concrete specimens containing fiber.

 

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Coronavirus disease 2019 (COVID-19) is a virally-induced pneumonia caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This is the third disease-causing coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and the middle east respiratory syndrome coronavirus (MERS-CoV) which has been known in the human population in the 21^st century. To this date (20^th of Mehr, 1399), more than thirty-four million people have been infected by this virus and more than a million have lost their lives because of it which further signifies the importance of COVID-19 prevention and treatment. In this review article, we first take a look at the history of the famous coronaviruses and then introduce the genetic and pathophysiology of SARS-CoV-2 in a detailed manner. After discussing the related clinical manifestations, we shed a light on the treatments that have been assessed to this date. In the end, we will briefly discuss the vaccines that are currency being developed and highlight their success rate, so far. It is delightful to assert that out own research team is currently developing an oral and/or respiratory vaccine against SARS-CoV-2 which is composed of spike-surface decorated chitosan nanoparticles.

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In today's, the preservation and maintenance of masonry structures in historical areas have become very important. A significant part of this issue is rooted in the use of non-reinforced construction materials in the building of such structures. In Iran, most of the historical buildings were built using masonry materials. The buildings were designed according to the special architecture of this region. The existing structures mostly consist of masonry walls as well as some openings with arched configurations. In these types of walls, the wall consists of two piers and an arch on top of them. Since Iran is located in a highly seismic zone, investigating the performance of these types of structures is essential under the action of earthquakes and lateral loadings. Therefore, in this paper, a numerical investigation is accomplished on the in-plane behavior of traditional brick arches under the action of lateral loads. To this end, the numerical model of a sample of an existing arch (in Kerman’s Mesgari bazaar) was considered. The model was developed on STKO software. In this regard, the nonlinear response of bricks and mortar joints was simulated by using the DamageTC3D material. As well, the geometry of the wall was constructed with four-node plane-stress elements. The lateral capacity of the wall was assessed under the action of gravity loads. To this end, the wall was analyzed under gravity loads with intensities of 0.0 to 0.2 MPa. Next, it was pushed laterally through the pushover analysis and the shear force-displacement capacity curve of the wall was obtained. Through a specific procedure, the obtained capacity curves were estimated with a bilinear graph. By using this graph, the performance points corresponding to the wall’s capacity were extracted and a complete discussion was made regarding the shear capacity and the corresponding displacement to each performance point. Based on the obtained results from the analysis, it was observed that with an increase in the intensity of the applied gravity load, the maximum shear capacity of the walls increases. However, a higher increase in gravity load intensity (over a specific limit) would cause more damage to the arch which leads to a smaller shear capacity. Also, it is observed that the distribution of cracks and their pattern along the walls follow a similar outline. However, crack widths are affected strongly by the intensity of the applied gravity load on the wall.
 

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Introduction: Gentamicin (GM) is a widely used aminoglycoside antibiotic. The nephrotoxicity of gentamicin causes reducing renal blood flow via vasoconstriction. Given PGE2's vasodilatory effects and the mechanisms of tissue damage in GM-induced nephrotoxicity, such as vasoconstriction, the aim of this study was to investigate the protective role of PGE2 in GM-induced nephrotoxicity. The diclofenac sodium was used to assess the direct effects of exogenous PGE2 by blocking endogenous production.
Materials and methods: The experiment was conducted on 56 male Wistar rats (200–250 g). Renal nephrotoxicity was induced by intraperitoneal (i.p.) injection of gentamicin (100 mg/kg). The therapeutic effects of PGE2 (0.2 µg/kg) and diclofenac (0.5 mg/kg) were assessed. The rats were placed in individual metabolic cages to collect urine. The systolic blood pressure and renal blood flow were measured. Levels of urea, creatinine, sodium, potassium, magnesium, and osmolarity were analyzed in plasma and urine samples. The left kidney was used for histological analysis.
 Results: Administration of gentamicin for eight consecutive days resulted in a significant increase (p<0.001) in serum creatinine, blood urea nitrogen (BUN), absolute sodium excretion (UNaV), and fractional excretion of sodium and potassium (FENa and FEK), while creatinine clearance, urine osmolarity, and renal blood flow significantly decreased (p<0.001) compared to the control group.
Treatment with PGE2 significantly reducing serum creatinine, UNaV, FENa, FEK (p<0.001), and BUN (p<0.05), while significantly increasing creatinine clearance, urine osmolarity, and renal blood flow (p<0.001).
Conclusion: Prostaglandin E2 provided substantial protective effects against gentamicin induced acute nephrotoxicity in rats.