فهرست مطالب mohammadmehdi heidari

B-cell acute lymphoblastic leukemia (B-ALL) is a complex disorder that includes multiple genetic changes, one of the main causes of which is rare and common chromosomal translocations that lead to abnormal gene fusions. This abnormal fusion produces a new protein that causes the leukemia cells. These types of rearrangements usually occur in lymphoma and result in the movement of genetic material between different chromosomes or within chromosomes. This systematic review aims to evaluate published studies and investigate the role and importance of common and rare chromosomal translocations in the occurrence of B-ALL.

This systematic review investigated and evaluated the evidence regarding the effect of chromosomal translocations in adults and pediatrics with B-ALL. This review was based on the preferred reporting items for systematic reviews and meta-analysis checklists. A literature search was conducted using international databases (such as PubMed, Web of Science, Scopus, Research Gate, Google Scholar, and Cochrane Systematic Reviews database). Only English-language articles published between January 2010 and January 2023 including MESH terms such as ALL, B-ALL, and chromosomal translocations were selected. Seventy-five related studies had the necessary criteria to be examined in the present study.

A total of 237 articles were retrieved in the online search. The excluded articles included research on other types of leukemia in adults and children, descriptive studies, case studies, studies related to animal models of leukemogenesis, and comparisons of common treatment methods of leukemia grouping cancers. Finally, seventy-five studies were identified as eligible for inclusion in this systematic review.

This review provides a comprehensive assessment of common and rare chromosomal translocations that can lead to the development of cancer cells. Chromosomal translocations play a role as diagnostic markers and important prognostic indicators and help specialists adjust treatment approaches according to their occurrence.

Productivity index is an index of effective, useful and efficient use of various resources. According to the standard of productivity and calculations of its related indicators, the correct way of effective use of production factors can be chosen considering the lack of resources and the need to improve competitiveness. On the other hand, the importance of realizing better productivity in the government sector is considered as one of the national goals of governments, and the study in this field, while showing its importance more than before, depicts the challenges and obstacles ahead. Therefore, examining and explaining productivity indicators has an important role in improving their efficiency and a support for the future plans of organizations. Considering the importance of the topic, in this research, the productivity indicators in the road, housing and urban development research center have been examined and explained. According to the activities of the Road, Housing and Urban Development Research Center, the specific productivity indicators of this research center include: 1- specific productivity indicators of the research sector (including research projects, laboratories and outputs) and 2- specific productivity indicators of the education sector (including training courses) internal colleagues, external training courses and holding conferences) and 3-specific productivity indicators of the executive sector (including employee productivity) which are extracted in this article.

Brain tumors are considered to be one of the most dangerous types of cancer, despite decades of research and treatment efforts. The activation of the telomerase enzyme is a critical factor in the immortality of these cells. Mutations in the promoter region of the TERT gene, particularly in the promoter hot spots, can influence the binding of activating transcription factors and inhibit the binding of negative regulatory factors of the TERT gene, ultimately regulating the gene's expression. This study aimed to identify and investigate the mutations of the TERT gene promoter region in glioblastoma, a malignant brain tumor, using bioinformatics.

A study was conducted using the case-control method where 35 patients with glioblastoma multiform brain tumor were examined along with 40 people who were examined as control samples. In this research, the Touchdown PCR technique and direct DNA sequencing were used to detect mutations in the promoter region of the TERT gene in patients with glioblastoma. Furthermore, bioinformatic analyses were conducted to investigate the pathogenic effect of nucleotide changes in this gene region.

In the core region of the TERT gene promoter, three-point mutations were identified (c.*146C>T، c.*144C>G and c.*143G>C). Two of these mutations were novel and have been observed for the first time in glioblastoma multiform. The remaining mutation was located in the promoter core's hot spot of the gene. This mutation was known as c.*146C>T.

In this research, the harmful impact of TERT promoter region mutations as a biomarker for glioblastoma was examined. These findings suggest that mutations in regulatory regions, as well as coding sequences, could be significant contributory factors in the process of carcinogenesis.

Tetralogy of Fallot (TOF) is one of infants' most common types of complex congenital heart defects (CHD). Several molecular mechanisms may play a role in its development, such as mutations in cardiac gene network components, cardiac gene regulatory pathways, dysfunction of cilia-expressing genes, and dysfunction of genes determining the left and right axis of the heart. The present study aimed to investigate the nucleotide changes of the CCDC103 gene and its relationship with CHD of the TOF type.

The present work was conducted for the first time in Iran as a case-control study on 85 children with TOF. The control group involved 56 healthy children without a family history of heart disorders. Touchdown polymerase chain reaction (PCR) and Sanger sequencing were used to evaluate point mutations in the CCDC103 gene. Moreover, bioinformatics databases were employed to predict the impact of nucleotide changes on protein structure and function.

A total of five heterozygous single nucleotide changes were detected in this gene (three missense mutations: p.S115R, p.C191R, p.M201V, a synonymous change without amino acid change, and a change in the 3'-UTR region). In addition, bioinformatics results predicted that p.C191R mutation is pathogenic and harmful.

The results indicated that in addition to the genes known in the pathogenesis of TOF, changes in the CCDC103 gene in the ciliary signaling pathway can play a role in causing heart defects.

Familial adenomatous polyposis (FAP) is a hereditary disorder that is the most common colon cancer syndrome in an autosomal dominant form. At first, germline mutations in the APC gene (adenomatous polyposis) were identified as the main genetic factor causing FAP, but during subsequent studies, the human MutY (MYH) gene with an autosomal recessive pattern was also identified as the factor causing this disease, which is commonly referred to as MutYH-dependent apoptosis (MAP). FAP and MAP present with an early onset of hundreds of adenomatous polyps in the colon, at a median age of 35–40 years, and are associated with a significantly increased risk of colon cancer (CRC). In some other patients, gastrointestinal polyps, congenital hypertrophy in the retinal pigment epithelium, desmid tumors, and extracolonic malignancies are seen. The common treatment method in patients is through endoscopic and surgical methods. However, the patients with FAP and their relatives should receive appropriate genetic counseling. The purpose of this review article was to describe and investigate the clinical aspects and genetic diseases of FAP and MAP. For this purpose, the latest articles related to FAP genetic disease were selected by searching Google Scholar and PubMed sources.

Despite the progress made in discovering the molecular mechanisms of FAP, its genetic factors are still not fully understood. A deeper understanding of the molecular biology and genetics of this disease can lead to healthy therapies that can be used to rezone intestinal polyps and neoplastic malignancies and be a new target for future treatment.

Piano key weir is a form of nonlinear weir designed to improve the discharge capacity of spillway structures. Due to the increase in effective length, they can be used in dam spillways or water regulation structures. It is modified form of labyrinth weir which easy to place on the existing spillway or newly constructed dam with less base area. There is no standard method available for PK weir design, and the amount of published information is insufficient for the design of PK weir. A large number of geometric and hydraulic parameters affect the discharge capacity of PK weir, and their effect on the hydraulic performance of the weir can be investigated with a numerical model or laboratory data. Simulation of flow over PKW using FLOW-3D software and the effect of the turbulence model on the accuracy of the numerical model is one of the goals of this study. Also, in this research, the effect of the ratio of the inlet key width to the outlet key width (Wi/Wo) and the effect of the energy head on the discharge capacity are investigated.

Laboratory data from Anderson (2011) were used to validate the numerical model. The total length and height of the weir are 4.848 and 0.197 m respectively, the floor slope in inlet and outlet key are 1:1.8, and number of keys is 4. The inlet and outlet key width are 0.116 and 0.925 m respectively, and the Wi/Wo ratio is 1.25. Selection of boundary conditions for the numerical model is one of the most basic stages of simulation. In order to define the boundary conditions, in the inflow point (Xmin) volume flow rate, in the sides of the weir (Ymin, Ymax) and bed (Zmin) wall condition, on the upper border (Zmax) symmetry condition and in the outflow section of the weir, outflow condition was used.

The numerical model results were compared with the laboratory data. The results showed that if the second order scheme and RNG k-ε turbulence model are used in the numerical model, the simulation accuracy of the flow over PKW increases. Also, the results show that increasing the He/P decreases the discharge coefficient. So that the discharge coefficient for He/P=0.92 decreases by about 50% compared to He/P=0.24. With the increase of the water depth on the weir, the interference of the flow takes place at the breaking point of the weir cycles, and as a result, the discharge coefficient decreases. Another factor affecting the flow coefficient of the piano key is the ratio of the inlet key width to the outlet key width. By increasing the Wi/Wo, the flow coefficient has increased, and then it becomes maximum at Wi/Wo=1.5.

In this research, the simulation of the flow over piano key and labyrinth weir was done using a numerical model. The results showed that for a fixed depth, the piano key weir passes more discharge than the labyrinth weir, and the ratio of flow through the piano key weir to the labyrinth weir is about 1.08. In other words, at a constant depth, the piano key weir passes 8% more flow. In this research, the effect of head energy on the discharge coefficient of the piano key weir was also investigated. The results show that increasing the He/P decreases the discharge coefficient. The results showed that if the Wi/Wo equal to 1.5, the highest discharge coefficient occurs for the piano key weir.

The maximum scour of the flip-bucket occurs at the jet landing site, so it is important to know the exact path of the jet. In this research, by building two laboratory models of different sizes, the ability to exist relationships in predicting the jet path, length, and coordinates of the jet peak was evaluated. According to the results, Kawakami's relation had better accuracy in predicting the jet path. The average error percentage of the jet trajectory length prediction in USBR and Attari relationships was less than 10% and other relationships were more than 20%. USBR, Attari, and Kawakami relationships had a good estimate of the jet trajectory length along the edge. The error of other relationships in estimating this characteristic was more than 30%. In predicting the horizontal distance of the high point of the jet trajectory, the theoretical relationship and the profile of Kawakami and USBR had an average error of less than 10%. Theoretical relationships, Kawakami and USBR in estimating the maximum height of the jet, have an estimate with an error of 23.7, 33.9, and 21.4% and according to the Nash-Sutcliffe criterion, none of these relationships have been able to get a very good category.

Nowadays, Box-Jenkins models are considered one of the applicable tools to forecast different time series, especially water table fluctuations. This study addresses the prediction of unit hydrograph fluctuations of Sahneh plain aquifer using Box-Jenkins models. The study area is Sahneh Plain located in the province of Kermanshah. Using monthly data related to 21 piezometers available in the plain, unit hydrograph time-series of Sahneh plain aquifer were computed and plotted for 19 water years (1991-92 to 2009-10). With the use of autocorrelation and partial autocorrelation functions, static time series of multiple seasonal Box-Jenkins models were fitted to the data. After reviewing the results, six top models were introduced. After verifying, ultimately, SARIMA (1,1,4)(3,1,0)12 model was chosen as a best one to forecast unit hydrograph fluctuations in the Sahneh aquifer. The results show that the selected model is capable of predicting seasonal fluctuations, but does not correctly represent the period or cycle.

Familial adenomatous polyposis (FAP) is a rare and hereditary disease in which multiple precancerous polyps develop in the patient's colon. Familial adenomatous polyposis is caused by mutations in the APC gene (5q21). According to new research, in addition to nuclear disorders, mitochondrial functional disorders are also one of the essential carcinogenic factors and also a promising target for cancer treatment. The aim of this study was to investigate the nucleotide changes of mitochondrial ATPase6 and MT-CYB genes in patients with FAP.

In this study, 9 Iranian families with Familial adenomatous polyposis were investigated to study mutations in mitochondrial genes. For this purpose, a fragment with the length of 558bp containing the ATPase6 gene and also a fragment containing the MT-CYB gene with a length of 853bp were studied using the Touchdown-PCR method and sequencing. Sequencing results were analyzed with several bioinformatics software and databases, including ExPASy, SIFT, PSIPRED, PolyPhen-2, I-Mutant, PROVEAN, PredictSNP, and PyMol.

In this research, five mutations were observed in the mitochondrial ATPase6 gene. Three mutations were synonymous (c.A8901G; p.L125L, c.C8958T; p.I144I and c.C8943T; p.P139P) and two non-synonymous mutations (c.T8780C; p.L85P and c.G9133A; p.E203K). Furthermore, two synonymous mutations (c.A15607G; p.K287K and c.C15833T; p.L363L) and one non-synonymous mutation (c.C15452A; p.L236I) were observed in the MT-CYB gene.

In this study, ATPase6 and MT-CYB genes were investigated in the patients with Familial adenomatous polyposis, and 5 and 3 mutations and nucleotide changes were observed in affected patients, respectively. Considering that mitochondrial genome mutations can play a role in tumorigenesis, identifying new mutations can be effective in early cancer diagnosis. More studies are needed to confirm the association between mitochondrial mutations and FAP disease.

Familial adenomatous polyposis (FAP) is an inherited disorder and a rare form of colorectal cancer. This disease appears equally in both sexes and its occurrence is more in the second or third decade of life. Mutations and alterations of the mitochondrial genome, especially the D-loop region, have been reported in various human tumors. But the exact role of these mutations in the pathogenesis and progression of tumors is still unclear. The purpose of the present study was to investigate the occurrence of mtDNA nucleotide mutations in the D-loop region, especially the hypervariable regions (HVR) in FAP patients.

In this case-control study, 56 FAP patients were investigated for mutations in the mitochondrial D-loop region by Touchdown PCR, single-stranded conformation polymorphism (SSCP), and sequencing analysis. Fisher's exact statistical tool was used to find the relationship between these nucleotide changes and the risk of FAP disease.

Nineteen nucleotide changes were identified in the D-loop region of patients with FAP symptoms. Two of these nucleotide changes (C16335T and C16352T) were novel and not previously reported in any disease. The results of the statistical analysis of observed mutations showed a statistically significant difference between the patient's group and the control group (p<0.05).

The findings of this study indicate a positive correlation of mtDNA mutations in the D-loop region in all FAP cases compared to the matched control groups. Therefore, the mutation in mitochondrial non-coding sequences may lead to the production of defective proteins in the respiratory chain by affecting the expression process of mitochondrial genes.

Cardiovascular diseases are currently the leading cause of death in the world. Arrhythmias are one of the most common cardiovascular diseases. In arrhythmia, the heartbeat becomes slow, fast, or irregular, which affects the efficiency of the heart, and in this case, the heart may not have enough ability to pump blood. Cardiac arrhythmias are the leading causes of sudden cardiac death in young people, affecting even patients with anatomically normal hearts. Arrhythmia syndromes are ion channel diseases that lead to abnormal electrical properties of the heart. This article examined the genetic causes affecting all types of cardiac arrhythmias. A detailed search was performed on Google Scholar and PubMed to identify research articles related to arrhythmia genetics. All duplicate articles based on the title and articles published before the year 2000 were removed during the screening. Finally, after several rounds of content review of the articles, 50 research articles were selected for this study.

It has been found that mutations cause arrhythmias in nuclear genes encoding membrane channels in heart muscle cells. However, the causes of some cases of arrhythmia are unclear and the possibility of multifactorial of these cardiac disorders is raised. The importance of this type of review article, while revealing the relationship between gene loci and types of arrhythmogenic syndromes, is to provide a molecular basis that can provide researchers with new diagnostic methods in addition to echocardiogram.

Ski jump as one of the energy dissipater systems at the end of weir has been considered by hydraulic engineers due to its cost-effectiveness. Despite the dissipation of a significant portion of the flow energy, the bed is subject to scouring and can pose hazards to the structure. In recent decades, equations have been proposed to estimate the scour rate of this structure, each of which has a specific problem. For example, in some of these relationships, there are some factors that affect scouring, such as the bucket radius or the lip angle of bucket. The equation of Azmatullah et al. Is one of the most complete relationships mentioned in most sources. In this equation, the depth of scour increases with increasing mean sediment size of bed materials, which contradicts previous research. In the present study, the neural network was trained to estimate the depth of scour and the transmission functions, number of layers and type of network training were optimally selected. Using neural network and sensitivity analysis, the effect of different variables on the scour depth was determined. A high-precision relationship was presented to predict the scour depth using explicit genetic programming

In order to investigate the scour depth in flip-bucket, a laboratory model with a width of 0.5 m, height of 45 cm, length of 59 cm, bucket radius of 15 cm and lip angle of bucket of 45 degrees was constructed. The flow rate through the laboratory model is 7 to 21.2 lit/s, head between upper reservoir water level and tail water level is 0.3 to 0.38 m, the tail water depth is 0.028 to 0.1 m and the D50 bed materials is 4.3 mm. In the present study, in addition to the measured laboratory data, used data related to the research of Azmatullah et al. In this study, neural network has been used to predict the depth of scour hole. The optimal structure of the neural network is affected by variables such as the number of neurons in the latent layer, the stimulus functions between the neurons, and the number of latent layers. In the present study, the optimal structure of the neural network was determined by trial and error. It should be noted that in this study, NeuroSolutions software was used for the architecture of the multilayer neural network of perceptron.

Stimulus functions, number of hidden layers and type of training are factors that affect the accuracy of the model. In this study, the optimal structure of the neural network was determined by considering the variables affecting network accuracy and using various laboratory data. The results show that if the number of hidden layers of a number is a function of hyperbolic tangent transfer and network training type, Levenberg-Marquardt, the accuracy of the neural network in estimating the maximum scour depth is better. Also in this study, the scour depth sensitivity index to discharge per unit width flow, upstream head, lip angle of bucket, bucket radius, tail water depth and mean sediment size were calculated. The sensitivity index of scour depth to discharge per unit of flow width, fall height and lip angle of bucket is more than zero and this shows that with the increase of these variables, the depth of the scour hole increases. In order to reduce the amount of scour holes, the depth of the tail water can be increased or a riprap can be used. According to the calculated sensitivity indices, if the depth of tail water or particle diameter increases by 10%, the maximum depth of the scour hole decreases by about 3.9 and 1.3, respectively. Depending on the economic considerations and the feasibility of each case, the appropriate option can be selected. In this study, using the data of Azmatullah et al. And using GEP software, a relationship was presented to estimate the maximum scour rate in the flip bucket, with an average error rate of 9.8% which shows the model's ability to estimate scour.

In this study a neural network model was given to estimate the depth of the scour hole in the flip bucket. The results show that if the number of hidden layers of a number is a function of hyperbolic tangent transfer and the type of network training is Levenberg-Marquardt, the neural network accuracy in estimating the maximum scour depth is better. Also in this study, the sensitivity index of scour depth to input variables was calculated. The greatest effect on the scour depth is related to the water discharge per unit width rate, if the flow rate increases by 10%, the maximum depth of the scour hole will increase by 8.5%. In this study, a relation was presented to estimate the depth of the erosion hole, the accuracy of which is evaluated very well according to the criteria. کلیدواژه‌ها [English]

The present study focuses on the effect of viscoelastic properties on the optimal design of pressurized irrigation system taking into account the impact of water hammer. For this purpose, the three models, the optimizer, the hydraulic steady solver (HSS), and hydraulic transient solver (HTS) were coded together in the form of a computer model. In the optimizer model, the initial population is created from the available diameters. Then, for each member of this population, in the HSS, the values of pressure in the nodes and velocity in the pipes are calculated. These values are sent to HTS as an initial condition. In the HTS, by applying a water hammer condition on the system, the maximum overpressure in each node is calculated and the results are sent to the optimizer model. Here the value of the objective function is calculated by observing the constraints for each member of the initial population and relative compatibility is obtained for all members. By applying the operation of mutation, intersection, replacement with the elitist approach, the next generation is finally calculated and the mentioned steps are repeated until the condition of stopping the calculations and determining the optimal answer is reached. Validation of the HTS in viscoelastic pipes using data measured at the Imperial College (London, UK) and considering three Kelvin–Voigt elements and retardation times of 0.05, 1.5 and 5 seconds for these three elements are done. The results showed that for wave speed of 390 m / s, the measured pressure fluctuations are in good agreement with the calculations. After confirming the model results, water hammer simulation of Ismailabad network in the current situation, which is composed of GRP and HDPE pipes, was performed with and without considering the viscoelastic properties for polyethylene pipes.

Abortion is a common complication that refers to the early termination of pregnancy with the death of the fetus before the 20th week of pregnancy. Previous studies show that many genes are involved in this disease, including the CX3CR1 gene, which is one of the inflammatory response genes in the immune system. The pathogenicity of these variants was determined in this study using bioinformatics analysis.

In this study, the effects of rs3732378 and rs3732379 mutation were predicted using bioinformatics tools including SIFT, PolyPhen2, PROVEAN, Predict SNP, and Exome Variant Server. Changes in the stability of mutant proteins were investigated using I-Mutant and DynaMut tools. Moreover, modeling of the protein structure, docking, and protein-ligand interaction were performed using SWISS-MODEL, SwissDock, and FRODOCK tools as well as PyMOL, Hawkdock, and MolSoft software, respectively.

Many polymorphisms related to the CX3CR1 gene have been known to date. Out of 244 missense mutations in the dbSNP database, two variants (rs3732378 and rs3732379) have been reported in association with recurrent pregnancy loss related to the CX3CR1 gene. The results of bioinformatics analyses showed that both variants were predicted as pathogenic mutations and changed the stability of the protein structure and played a key role in interaction with the ligand.

The findings of this study indicate that two missense mutations in the CX3CR1 gene are an important candidate for recurrent miscarriage and their identification in patients with recurrent miscarriage can be regarded as a risk factor.

One of the most common causes of male infertility is Varicocele abnormality. Men with a family history of varicocele are at higher risk for these disorders. As a result, genetic and molecular factors may play an important role in the pathogenesis of varicocele associated with infertility. Therefore, this review study was performed with aim to investigate the role of candidate genes and their molecular mechanisms and the role of genetics in the development or exacerbation of varicocele.

In this review article, to find the related studies, the Latin (PubMed, Google Scholar) and Persian (SID and Magiran) databases were searched without time limitation in a period of 4 years using the keywords of "Varicocele, Male Infertility and Gene".

Mutations or polymorphisms of probable candidate genes including GST, TNP1,2, hoGG1, NOS3, MTHFR ACP1, P53 and POLG have different effects on sperm, spermatogenesis and varicocele in general.

So far, several genes have been investigated as possible candidates for the occurrence and progression of varicocele in different populations of the world, each of which has shown various effects on the pathophysiology of varicocele. Therefore, the correctness or wrongness of the hypothesis (the effect of genetics on varicocele) is still unclear due to the lack of coordination of evidence.
 

As for the severe limitation of water resources, costly construction and operation of water supply systems and rapid population growth, the optimal design of these networks is essential. The problem of cost minimization is done by minimizing the diameter of the network pipes, which reduces the pressure in the network. Since providing adequate pressure in the nodes is one of the important design principles, so in this study, the problem of optimization in several sample networks was defined with the objectives of minimizing the cost and lack of pressure in the whole network. EPANET software was used for hydraulic analysis of sample networks and the multi-objective optimization process through coding of PESA-II and SPEA-II algorithms in MATLAB software and their connection to EPANET face Took. The cost function was initially defined only by considering the relationship between cost, diameter, and pipe length. Then, in the next definition, the cost of exceeding the allowable pressure range, where the minimum and maximum allowable pressures are 30 and 60 meters, respectively, was added to this function, and the program again with the number of repetitions that ended in the best answer Was implemented. The results showed that these algorithms have a high ability to find optimal solutions. In these algorithms, considering the cost of exceeding the allowable pressure limits results in the best answer that other researchers have ever obtained for sample networks, which for the two-loop and lansey network, The cost was 419000 and 1069393 $ respectively, and the pressure shortage was zero and with a low number of iterations, in the two-loop network for both algorithms with 20 iterations and in the lansey network for PESA-II and SPEA-II algorithms  with 200 and 140 iterations respectively, to achieve a higher number of optimal answers and the time to achieve convergence is significantly reduced, so that in the two-loop network, the execution time of PESA-II and SPEA-II algorithms are 0.55 and 0.59 minutes respectively, and in the lansey network It was 1/8 and 7.4 minutes respectively.

In most practical hydraulic engineering problems, accurate flow measurements are required. Understanding flow quantities is an important point in water resources management. Therefore, providing the most appropriate velocity distribution estimation relation that is consistent with the measurement data has always been of interest to researchers. With the development of entropy theory, these methods have been used in a wide range of engineering sciences, including hydraulics and fluid mechanics. In the present study, using the Renyi entropy method, the effective parameter "m" on the Renyi entropy parameter "G" was investigated and the velocity distribution in a circular pipe in the conditions that 36.2, 50, and 70% of the circular pipe fills. It was estimated at two points by measuring the velocity at depths (0.1D-0.9D), (0.2D-0.8D), and (0.3D-0.7D) relative to the water level. In order to determine the accuracy of estimating the velocity distribution using the Renyi method, the correlation coefficient and the root mean square error was used and also to determine the accuracy of entropy parameters, normalized root mean square error was used. The results showed that the Renyi entropy method has high accuracy with observational data. Also, velocity measurement at depth (0.9D-0.1D) from the water surface for 36.2, 50, and 70% of the circular pipe, with the normalized root mean square error to 0.2325, 2.36, and 0.51 respectively, has higher accuracy.

Proper design of technical and hydraulic parameters plays an essential role in the success of a pressurized irrigation or urban water distribution project and its economy. Therefore, engineers should be able to select the best solution in different stages in terms of design, construction, maintenance and operation according to the existing limitations and make the necessary decisions.The ultimate objective of such decisions is to minimize costs or maximize benefits by considering limitations.The objectives defined for each system may be different but it is certain that in today's engineering world, one-sided objectives are never defined.Today, meta-exploration optimization methods for the optimal design of irrigation and water supply networks have been considered.It is not possible to compare one-objective and two-objective methods in appearance. But in the two-objective method, one of the objectives is defined in such a way that it eventually goes to zero this comparison is possible.

Hence in the present study, the optimal design of a pressurized network with one-objective binary genetic algorithm and two- objective NSGAII has been done.Genetic algorithm is a method that evaluates different designs through trial and error with analogy criteria and maintains the best designs and eventually achieves the proper design. Multi-objective optimization is a sub-branch of the MCDM multi-criteria decision-making set that takes place among an unlimited set of possible solutions. In such cases unlike single-objective optimization problems, due to the existence of several conflicting goals, a set of answers is obtained instead of just one answer. In order to compare the two methods in terms of accuracy of results and speed of calculations the second objective function in NSGA-II was defined as the sum of the pressure deficiencies in the network. Observance of minimum pressure constraints in the network causes the value of this objective function to reach zero and the results of the two methods are comparable. In order to analyze the network and obtain the pipe flow and pressure in the system nodes, the matrix shape of the gradient method was used. Computer code was developed for single-objective (GA) and multi-objective (NSGAII) optimization methods in VB programming environment. Also, the simulation code according to the matrix shape of the gradient method was prepared in this programming environment. Finally, All the codes were linked to each other.

In order to validate the NSGA-II developed cod, its ability to solve several constrained and none- constrained multi-objective mathematical problems was proposed. The results showed that there is a very good agreement between the results of the present model and the results presented by previous researchers. In order to validate the genetic algorithm model, the model was used to solve the linear and nonlinear constrained optimizations problems that have analytical solutions. it has been shown that the results obtained from the model are exactly equal to the results of analytical solutions. After verifying the prepared codes from a programming point of view, a proposed two-loop network consisting of 7 pipes and 8 nodes whit one earth reservoir was designed with both GA and NSGA-II algorithms. The result showed, estimated cost of implementing the studied network by tow method was the same and with a difference of less than 1%, while the cost of calculations in NSGA-II method was estimated to be about 2% of the genetic algorithm method. That is, the time to reach the optimal answer in NSGA-II method is 50 times faster than GA method.

Given that the cost of calculations in the NSGA-II method is much lower than the GA method, the use of this method to optimal design of water presuurized network is recommended, Provided that in this method the second objective function is defined in such a way that if all the constraints are observed, its value will be close to zero. For this purpose, the objective function of the sum of pressure deficiencies Was deemed appropriate.

There are various methods to prevent the entry of suspended sediments into the irrigation canals, one of which is the construction of sedimentation ponds at the beginning of the irrigation network. Sediment efficiency, which is the ratio of the concentration of outlet sediments to inlet, should be determined before designing the sedimentation pond according to the geometric dimensions of the structure, hydraulic properties and characteristics of inlet sediments to be planned for management and operation. The purpose of this study is to present a one-dimensional model of sedimentation in the sedimentation pond by considering the sedimentation of inlet sediments, which in addition to estimating the trapping efficiency in the pond, also calculates changes in the pond floor, sedimentation of sediment outlet and sediment concentration in each section.

n this study, in order to simulate sedimentation in the sedimentation pond, first a numerical model was developed and then the effect of the geometric factors of the pond on the sediment trapping efficiency was investigated. In the developed one-dimensional numerical model, the governing equations of flow and sediment were solved, respectively. To validate the results of the numerical model, El-Baroudi (1969) laboratory data were used, which include a rectangular sedimentation pond with a length of 1.2446 m and a width of 0.4572 m. For different discharges, El-Baroudi deposited 200 mg/l of sediment with a specified diameter into the sedimentation pond and after a certain period of time measured the concentration of the effluent from the pond. Also, field data of Nekoabad sediment catchment area of Isfahan (Shetab-Boushehri et al., 2010) were used for validation.

The results of trap efficiency verifications showed that the mean value of the square root of the mean square error of the numerical model for El-Baroudi (1969) experiments was 6.15% and for the left and right sedimentation ponds were 8.13 and 6.77%, respectively. Also, the trapping efficiency was investigated for all sediment particles and for each group of particles in relation to the length of the pond. The results showed that with increasing the distance from the beginning of the pond, the amount of sedimentation efficiency increases so that at the end of the pond The sediments are deposited in the left and right basins, respectively. The floor level of the sedimentation pond also changes due to sedimentation of sediments. The rate of these changes in the floor of sedimentation ponds at the beginning of the structure is higher than the end due to the high concentration of inlet sediments. The amount of these changes in the bottom of the left and right sedimentation ponds using the numerical model simulation of the present study after three months was about 23.4 and 20 cm, respectively.

After developing and validating the numerical model, the performance of Nekoabad sedimentation ponds and El-Baroudi laboratory model were investigated using the numerical model. The results showed that the average sediment trapping efficiency for the left and right sedimentation ponds was 36.5% and 27.3%. Therefore, a large amount of sediment enters the irrigation network. In order to improve Nekoabad sedimentation ponds and increase sediment trapping efficiency, the length, width or depth of the pond can be increased. For this purpose, by increasing one of the above variables and keeping the other parameters constant, the numerical model was executed and the trapping efficiency was calculated. The results showed that increasing the length of the left sedimentation pond and increasing the width of the right pond of Nekoabad Dam has the greatest effect on the trapping efficiency.

CDKN2A, encoding two important tumor suppressor proteins p16 and p14, is a tumor suppressor gene. Mutations in this gene and subsequently the defect in p16 and p14 proteins lead to the downregulation of RB1/p53 and cancer malignancy. To identify the structural and functional effects of mutations, various powerful bioinformatics tools are available. The aim of this study is the identification of high-risk non-synonymous single nucleotide variants in the CDKN2A gene via bioinformatics tools.

Among the identified polymorphisms in this gene, 353 missense variants are retrieved from the national center for biotechnology information/single nucleotide polymorphism database (NCBI/dbSNP). Then, the pathogenicity of missense variants are considered using different bioinformatics tools. The stability of these mutant proteins, conservation of amino acids and the secondary and tertiary structural changes are analyzed by bioinformatics tools. After the identification of high-risk mutations, the changes in the hydrophobicity of high-risk amino acid substitutions are considered.

Deleterious single nucleotide polymorphisms (SNPs) were screened step by step using the bioinformatics tools. The results obtained from the set of bioinformatics tools identify high-risk mutations in CDKN2A gene.

18 high-risk mutations including L16R/Q, G23D/R/S, L32P, N42K, G55D, G67D/R, P81R, H83R, G89D/S, A102E, G101R, G122R, and V126D were identified. According to the previous experimental studies, the association of L16R, G23D/R/S, L32P, G67R, H83R, G89D, G101R, and V126D amino acid substitutions with various cancers has been confirmed.

Due to the water shortage in developing countries, increasing the hydraulic performance and increasing the efficiency of water distribution in irrigation networks is necessary. One of the strategies for improving the efficiency of agricultural water productivity is increasing the accuracy of discharge measurement and controlling the water level. Gates are needed in order to control the amount of water released from dams and for regulating the water level in irrigation networks. There are different types of gates and the most common types of gates are sluice gates and radial gates. Gates are used widely in irrigation networks; therefore choosing small dimensions for the gates can reduce the channel costs. One of the ways for reducing the dimensions of the gate is to create a sill at the bottom of the canal and install the gate on the sill, so the design height of gate is reduced and it’s economically affordable. Estimation of the discharge coefficient of gate and consequently the amount of flow is one of the most important issues in hydraulic. The coefficient of discharge for free flow radial gates without the sill depends on the upstream water level and the gate opening (Bos, 1989). The objective of this paper is to investigate the effect of characteristics of sill such as the shape, height and location on the discharge coefficient for free flow radial gates. To achieve this goal, first the Flow-3D model’s output results for simulation of flow passing through a radial gate are validated using the experimental data and then the effect of the sill on the flow passing through a gate is examined.

Nuclear genetic mutations have been extensively investigated in solid tumors. However, the role of the mitochondrial genome remains uncertain. Since the metabolism of solid tumors is associated with aerobic glycolysis and high lactate production, tumors may have mitochondrial dysfunctions. Familial adenomatous polyposis (FAP) is a rare form of colorectal cancer and an autosomal dominant inherited condition that is characterized by the progress of numerous adenomatous polyps in the rectum and colon. The present study aimed at understanding the nature and effect of mitochondrial cytochrome c oxidase subunit 2 (COII) gene mutations in FAP tumorigenesis. Fifty-six (26 familial and 30 sporadic) FAP patients and 60 normal controls were enrolled in this study. COII point mutations were evaluated by PCR and direct sequencing methods, and a total of 7 mtDNA mutations were detected (3 missense, 1 nonsense, and 3 synonymous variations). Novel nonsynonymous COII gene mutations were mostly in heteroplasmic state. These mutations change amino acid residues in the N-terminal and C-terminal regions of COXII. Bioinformatics analysis and three-dimensional structural modeling predicted that these missense and nonsense mutations have functional importance, and mainly affected on cytochrome c oxidase (complex IV). Also, FAP patients carried a meaningfully higher prevalence of mutations in the COII gene in comparison with healthy controls (P <0.001). Analysis of cancerassociated mtDNA mutation could be an invaluable tool for molecular assessment of FAP so that these findings can be helpful for the development of potential new biomarkers in the diagnosis of cancer for future clinical assessments.

Congenital central hypothyroidism (CCH) is a rare autosomal recessive disease caused by mutations in the thyroid-stimulating hormone β subunit (TSHβ) gene. Since patients with CCH do not experience increased serum levels of TSH, the diagnosis is usually delayed, which leads to negative consequences in the neonatal TSH screening. Genetic diagnostic studies enable us to identify affected relatives at high risk for rapid diagnosis and treatment of the disorder.

This study aimed to investigate genetic variations in the TSHβ gene for the first time in Iranian patients with CCH.

Seven children affected by congenital TSH-deficient hypothyroidism were investigated for mutations in TSHβ. Variable TSH levels in these patients ranged from low values for diagnosis to significant values, so central hypothyroidism was assumed due to mutations in the TSHβ gene.

We identified two novel heterozygous (F11Y and G106R) and one homozygous (T14A) missense mutations in the coding sequence of exons 2 and 3. One of the new heterozygous mutations (F11Y) and a homozygous (T14A) missense mutation were found in exon 2 of the TSHß-subunit gene. The novel mutation G106R in exon 3 was found in three pediatric patients with congenital hypothyroidism. c.40A > G (T14A, rs10776792) appears to be the most common genetic variation associated with TSH deficiency. The others were c.32T > A in exon 2 and c.316G > C in exon 3, which resulted in a change from phenylalanine to tyrosine (p.F11Y) and glycine to arginine (G106R), respectively.

The identification of these mutations for the first time in Iranian patients suggests that CCH is more common than previously recognized, and the TSHβ gene may be the mutational hot spot.

Atherosclerosis is the important cause of most cardiovascular diseases, with high prevalence and mortality. Atherosclerosis is not only a lipid metabolism disorder but also recently is defined as a chronic inflammatory disease. Several studies showed that interleukin-6 (IL-6) is involved in the pathogenesis of atherosclerosis. The aim of the present study is the examination of IL6 mRNA Levels and hypomethylation of IL6 promoter in atherosclerosis patients.

In this assay, a total of 35 cases with atherosclerosis and 30 controls were enrolled. RNA and DNA were isolated from the peripheral blood of all samples. Mean IL6 gene expression was determined by RT-PCR and methylation status at six CpG motifs in IL6 promoter was determined using bisulfite genomic sequencing.

Real Time-PCR analysis results showed the mean IL6 RNA level in atherosclerosis patients candidate for CABG (coronary artery bypass grafting) was significantly higher than controls (P value = 0.01). Also, the upstream CpG motifs (-1038 to -952) in IL6 promoter were predominantly unmethylated in patients than in the controls (P value = 0.01).

These findings suggest that an increase in IL-6 gene expression and its DNA hypomethylation promoter are associated with atherosclerosis patient’s candidate for CABG surgery.

The diversion dams are used to increase the water level and diversion flow from the river to intakes. Increasing the water level in the river will increase the potential flow energy upstream of the dam, as a result, the flow velocity on the overflow increases. Flow at the toe of a spillway is supercritical. If the high energy of water does not dissipated, causing scouring of the river's materials. Therefore, stilling basins are usually used to dissipate the energy of water exiting the spillway of a dam. If the flow energy is high in the toe, the stilling basins will have a larger dimension and the cost of the design will increase. Information about how to change the speed and depth of the flow during the spillway and calculating the flow characteristics in the in the toe of a dam is the most important factor in determining the type and dimensions of the stilling basins. Few studies have been conducted on the amount of energy loss and the flow characteristics in the toe of the dam. One of the objectives of this study is to provide an appropriate Formula for determining the amount of energy depreciation on the spillway that can be used to calculate the amount of depth and flow velocity in the toe of the dam. Investigation of the effect of surface roughness on discharge coefficient, flow velocity profile and the energy dissipation rate are other goals of this research.

In this paper, Savage and Johnson’s (2001) experimental data were used for evaluating the accuracy of the FLUENT model results. A physical model of a typical ogee spillway, with a design head Hd of 301 mm was fabricated and tested at the UWRL. The model was constructed of Plexiglas and was fabricated to conform to the distinctive shape of an ogee crest. The model also included a tangent section and a typical flip bucket. Plexiglas was chosen because it could be fabricated with smooth curves and easily instrumented with pressure taps. The model was 1.83 m wide and approximately 0.80 m high. The P/Hd ratio (height of crest/design head) was 2.7. Wall boundary condition was applied to the spillway body and vertical walls and floor of reservoir. Zero pressure boundary condition is applied in output and upper flow field. Zero pressure is applied in air inlet and velocity inlet in upstream boundary. VOF (volume of fluid) was used to determine free surface for solving flow field and to determine boundary condition of two-phase flow. The value of volume fraction is considered equal to zero on all boundaries, except that the water inlet flow value is applied equal to one. Using available experimental data, the depth of water on the weir crest and the pressure on the overflow body were calculated and compared with the observed results. In order to study the effect of bed roughness on velocity profile, flow coefficient and energy loss, the values of 0.01, 1 and 3 mm were considered for roughness and the FLUENT model was again applied for these values. By performing some simulations, relation to energy loss over ogee spillway was presented.

Based on the simulations carried out by the FLUENT model, the k-ε RNG turbulence model and the PISO algorithm are suitable for separating the governing equations. The water depth and pressure on spillway calculated by the FLUENT model is very close to the observed data. The average relative errors of the numerical model in estimating the water depth is 3.35% and average errors in estimating pressure on spillway are 0.88, 1.22 and 1.51cm for Q/Qd=1.33,1,0.625 respectively, which are suitable for predicting the characteristics of flow passing through a ogee spillway. Comparison of the results of the numerical model and observational values shows that the correlation coefficient of the pressure data is about 97.5%, which indicates the proper accuracy for simulating the flow through the overflow. One of the factors influencing the characteristics of the flow through the overflow is the body roughness. The discharge flow rate decreases slightly as surface roughness height and maximum velocity at any section is slightly decreasing as the surface roughness.

The results show that with increasing roughness of the weir crest at low discharge, about 6% of the discharge coefficient decreases compared to the smooth state. Also, with an increase in roughness at low discharge, about 50 percent of the energy in the toe of a spillway is reduced. In this study, a relationship was also proposed for the amount of energy loss over ogee spillway, which provides an accurate precision for calculating the amount of energy at the beginning of the stilling basins.