A sustainable approach for site selection of underground hydrogen storage facilities using fuzzy-delphi methodology

One of the consequences of rapid global population growth is the increase in the energy demand. Currently, the main source of energy for various applications is fossil fuels, which are not renewable and their utilization at large scales have caused a number of environmental issues such as global warming. Hydrogen is one of the main renewable energy sources; however, its utilization has not yet been sufficiently commercialized due to some existing technical issues. For large-scale underground Hydrogen storage facilities, selecting the most suitable set-up location is accounted to be a crucial factor in order to use Hydrogen as a promising and environmentally friendly energy carrier. This study aims to develop an expert judgment approach for the prioritization of criteria involving site selection of large-scale Hydrogen storage facilities to support development of modern cities and industries. In this regard, Fuzzy-Delphi methodology was used to prioritize the criteria and sub-criteria, which seemed to be most relevant for the underground Hydrogen storage site selection process. A comprehensive screening was performed in the literature and eighteen criteria from technical, economic, health, safety and environment (HST) and social points of view were extracted. A professional questionnaire was designed for the criteria prioritization and SPSS 25.0 was employed to analyse the achieved results. According to the gained results, the most important sub-criteria were identified as legal restrictions, reservoir permeability and porosity, and regional risks. Also, the findings demonstrated that HSE and technical issues of sustainability for the site selection of H2 underground storage were more underscored in comparison to economic and social criteria. It is concluded that more in-depth studies are still needed to cover more aspects of sustainability regarding site selection for underground gas storages with special focus on social dimensions.publishersversionpublishe

Metabolic Engineering of Escherichia coli for para-Amino-Phenylethanol and para-Amino-Phenylacetic Acid Biosynthesis

Aromatic amines are an important class of chemicals which are used as building blocks for the synthesis of polymers and pharmaceuticals. In this study we establish a de novo pathway for the biosynthesis of the aromatic amines para-amino-phenylethanol (PAPE) and para-amino-phenylacetic acid (4-APA) in Escherichia coli. We combined a synthetic para-amino-l-phenylalanine pathway with the fungal Ehrlich pathway. Therefore, we overexpressed the heterologous genes encoding 4-amino-4-deoxychorismate synthase (pabAB from Corynebacterium glutamicum), 4-amino-4-deoxychorismate mutase and 4-amino-4-deoxyprephenate dehydrogenase (papB and papC from Streptomyces venezuelae) and ThDP-dependent keto-acid decarboxylase (aro10 from Saccharomyces cerevisiae) in E. coli. The resulting para-amino-phenylacetaldehyde either was reduced to PAPE or oxidized to 4-APA. The wild type strain E. coli LJ110 with a plasmid carrying these four genes produced (in shake flask cultures) 11 ± 1.5 mg l−1 of PAPE from glucose (4.5 g l−1). By the additional cloning and expression of feaB (phenylacetaldehyde dehydrogenase from E. coli) 36 ± 5 mg l−1 of 4-APA were obtained from 4.5 g l−1 glucose. Competing reactions, such as the genes for aminotransferases (aspC and tyrB) or for biosynthesis of L-phenylalanine and L-tyrosine (pheA, tyrA) and for the regulator TyrR were removed. Additionally, the E. coli genes aroFBL were cloned and expressed from a second plasmid. The best producer strains of E. coli showed improved formation of PAPE and 4-APA, respectively. Plasmid-borne expression of an aldehyde reductase (yahK from E. coli) gave best values for PAPE production, whereas feaB-overexpression led to best values for 4-APA. In fed-batch cultivation, the best producer strains achieved 2.5 ± 0.15 g l−1 of PAPE from glucose (11% C mol mol-1 glucose) and 3.4 ± 0.3 g l−1 of 4-APA (17% C mol mol−1 glucose), respectively which are the highest values for recombinant strains reported so far

Chemical composition and antibacterial activity of some herbal essential oils against Streptococcus mutans

Background and aims: One of the most common chronic diseases in the world is tooth decay. A variety of bacteria are involved in this disorder of which Streptococcus mutants is the most common. Essential oils are considered as new natural compounds for use in combating drug-resistant bacteria. This study was aimed to evaluate the antibacterial activity of some essential oils prepared from Eucalyptus caesia Benth, Cuminum cyminum L. and Satureja hortensis L. on S. mutants. Methods: In this study, essential oils were extracted by hydrodistillation method. E. caesia Benth, C. cyminum L. and S. hortensis L. were characterized by using gas chromatography‒mass spectrophotometry (GC‒MS). Antibacterial activity indices including minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and zone of inhibition for the above essential oils against Streptococcus mutans were determined using broth macro-dilution and disk diffusion methods. Data analysis was performed using one-way ANOVA and Tukey test. Results:Results showed that all three extracts had antibacterial activity against S. mutants. S. hortensis L. essential oil with the lowest MIC and MBC value (13.2 and 18.4 µg/ml, respectively) and the biggest inhibition zone showed the strongest antibacterial effect against S. mutants in all exposure times and at all concentrations, compared with two other essential oils. Furthermore, C. cyminum L. essential oil had higher anti-bacterial activity against S. mutant than E. caesia Benth essential oil. Conclusions:The essential oils used in the present study with different components showed antibacterial activity (especially S. hortensis L essential oil), and therefore they can be used as a new antibacterial substance. Keywords: Dental caries, Streptococcus mutans, Essential oils, Antimicrobial

Biological and physiological characteristics of human cumulus cell in adherent culture condition

Background: Cumulus cells, as oocyte nurse cells, provide a suitable microenvironment with growth factors and cellular interactions required for oocyte maturation. Thus, these cells may serve as a natural niche for in vitro studies of female germ cell development. Cumulus cells may help attain a better understanding of the causes of infertility in women and eventually improve the outcomes of cases that respond poorly to standard infertility treatment. Objective: The aim of this study was to isolate, culture, and investigate the biological characteristics of human cumulus cells. Materials and Methods: In this experimental study, cumulus cells were isolated, cultured, and characterized using reverse transcription-polymerase chain reaction analyses of specific genes including FOXL2, CYP19A1, FSHR, AMHR, and LHR. The presence of vimentin, a structural protein, was examined via immunofluorescent staining. Moreover, levels of anti-mullerian hormone (AMH) and progesterone secretion by cumulus cells were measured with ELISA after 2, 4, 12, 24, and 48 hr of culture. Results: In adherent culture, human cumulus cells expressed specific genes and markers as well as secreted AMH and progesterone into the medium. Conclusion: Cumulus cells secrete AMH and progesterone in an adherent culture and might be applicable for in vitro maturation (IVM) and in vitro gametogenesis (IVG) studies. Key words: Cumulus cells, Conditioned medium, In vitro maturation, In vitro gametogenesis, Niche

Is Decline Rate of Intact Parathyroid Hormone Level a Reliable Criterion for Early Discharge of Patients after Total Thyroidectomy?

Introduction: Parathyroid dysfunction leading to symptomatic hypocalcemia is not uncommon following a total thyroidectomy and is often associated with significant patient morbidity and a prolonged hospital stay. The current study aimed at evaluating the comparative predictive role of serum calcium and intact parathyroid hormone (iPTH) for post-thyroidectomy hypocalcemia.   Materials and Methods: This prospective study was performed in 83 consecutive patients undergoing total thyroidectomy. Laboratory data such as serum calcium, vitamin D level, serum iPTH and serum phosphorus levels before surgery, postoperative calcium, and PTH levels measured after 1 and 6 hours and on the first postoperative day (1POD) were recorded.   Results: Among the 83 patients, the mean (SD) age was 45.87 (12.57) years (range, 21–72 years); 70 (84.3%) patients were female. Final pathology was benign for 47 (56.6%) patients and malignant for 36 (43.4%) patients. In total, lymph node dissections were performed in 19 subjects (22.9%). On histological examination of the specimens, the parathyroid gland was found to have been removed inadvertently in 13 (15.7%) cases. In total, 35 (40.9%) patients developed hypocalcemia after thyroidectomy; receiver operating characteristic (ROC) analysis showed that a cut-off value of 15.39 pg/ml for iPTH, with a decline rate of 73% 1 hour after thyroidectomy is a significant predictor of hypocalcemia (area under the curve [AUC], 0.878; 95% confidence interval [CI], 0.79–0.96,

Evaluation of Salinity Tolerance of Alfalfa Genotypes during Germination Stage Using Multivariate Analysis

ABSTRACT Alfalfa is one of the most important forage plants with a special position among crops. Germination is one of the most sensitive stages to environmental stresses in crops. Therefore, to evaluate and select the most tolerant genotypes to salinity stress during germination stage, 20 genotypes of alfalfa were compared to each other in a completely randomized design. Four salinity levels including 0 (control), 75, 150, and 225 mM NaCl were applied. Analysis of variance showed significant difference for studied characteristics and indices among salinity stress levels and different genotypes. Principal component analysis using all measured characteristics under salinity stress showed that Nikshahri, Bami, Mesa-Sira, Gomi, Sahandava, Hamedani, Kodi, and Siriver were tolerant genotypes to salinity and Defi, Melissa, Kaiseri, Gargologh, and Diablo verdewere sensitive genotypes to salinity. Cluster analysis using the studied characteristics led to the classification of genotypes into two clusters. The first cluster (salinity tolerant) included Nikshahri, Hamedani, Yazdi, Baghdadi, Bami, Gomi, Kodi, Rahnani, Mesa-Sira, kf15, Sahandava, and Siriver genotypes and the second cluster (sensitive to salinity) involved Defi, Melissa, Kaiseri, Gargologh, Ramandi, Dastgerd, Harpinger, and Diablo verde genotypes

Biotechnologische Produktion von aromatischen Aminen und aromatischen Alkoholen durch rekombinante Escherichia coli-Stämme

Aromatic amine (AA) are an important group of industrial chemicals which are widely used for technical and pharmaceutical applications and described as the building block of drugs (Bedair et al. 2006; Jobdevairakkam and Velladurai 2009; Sacco and Bientinesi 2016), antibiotics, plastics and aromatic polymers (Arora 2015; Masuo et al. 2016; Tsuge et al. 2016; Kawasaki et al. 2018). In addition, aromatic alcohols, as other valuable compounds, are widely used in manufacturers of perfumes, cosmetics, and foods, and pharmaceutical industry (Etschmann et al. 2002; Miró-Casas et al. 2003; Bai et al. 2014). Most of the AAs and aromatic alcohols are chemically synthesized from petroleum sources and considered as “unnatural”, which are inappropriate to make cosmetic, drugs or food ingredient, thereby natural microbial biosynthesis of these valuable compounds in E.coli would be an alternative approach. In the first part of this study, a de-novo biosynthesis pathway was established for high titer production of three aromatic amines, para-amino-L-phenylalanine (L-PAPA), para-amino-phenylethanol (PAPE) and para-amino-phenylacetic acid (4-APA) from glucose/glycerol via genetic modification of the shikimate pathway in recombinant E. coli (Mohammadi et al. 2018 and 2019). To generate a platform strain for L-PAPA production from shikimate pathway, the genes pabAB from Corynebacterium glutamicum (Kozak 2006), papB and papC from Streptomyces venezuelae (Blanc et al. 1997; He et al. 2001; Mehl et al. 2003) were heterologously overexpressed from plasmid in E. coli FUS4.7R (Gottlieb et al. 2014). Then, the metabolic flux was directed to PAPE and 4-APA production via overexpression of aro10 from Saccharomyces cerevisiae (Kneen et al. 2011; Vuralhan et al. 2003 and 2005) and both aro10 and feaB in E. coli FUS4BCR, respectively. The engineered E. coli strains were cultured in the shake-flasks with fed batch condition and investigated for L-PAPA, PAPE and 4-APA production by HPLC and LC-MS. In the simple shake flask experiments, the plasmid based strain produced L-PAPA as high as 0.534 ± 0.024 g l-1 from 5 ± 0.24 g l-1 glycerol. Also, introduction of aro10 and yahK in L-PAPA producing strain resulted in 0.526 ± 0.025 g l-1 PAPE. Furthermore, by introducing feaB into the PAPE- producing strain, 4-APA was obtained with a titer of 0.458 ± 0.014 g l-1. Last but not least, by further strain improvement and optimizing growth condition via glucose/glycerol feed strategy, an increasing titer of L-PAPA, PAPE and 4-APA approximately 5.5 ± 0.4 g l-1, 2.5 ± 0.15 g l-1 and 3.4 ± 0.3 g l-1 were obtained, respectively. In subsequent fed-batch cultivation with a final volume of 12.2 l and the carbon sources glycerol, a final L-PAPA-titer of 16.8 g l-1 was obtained. This equals a yield of 0.13 L-PAPA / glycerol (g g-1) and a space-time-yield of 0.22 g l-1 h-1 L-PAPA formation over the whole process. Furthermore, a de-novo biosynthesis pathway for the production of 2-Phenylethanol (2-PE)/tyrosol from glucose with genetically engineered E. coli strains without additional L-phenylalanine/ L-tyrosine as supplement was demonstrated. Starting from chorismate, which is the direct precursor of phenylpyruvate (PP)/ 4-Hydroxyphenylpyruvate (4-HPP), an artificial Ehrlich biosynthesis pathway was created (Etschmann et al. 2002) toward 2-PE or tyrosol. To generate a platform strain for production of 2-PE and tyrosol from shikimate pathway, the genes pheA or tyrA encoding proteins chorismate mutase/prephenate dehydratase or prephenate dehydrogenase (feedback resistance variant, Rüffer et al. 2004; Gottlieb et al. 2014), respectively, were cloned and subsequently overexpressed from plasmid in E. coli. In the next step, the metabolic flux was directed to 2-PE and tyrosol production via overexpression of aro10 encoding phenylpyruvate decarboxylase from S. cerevisiae. Furthermore, in order to enhance the flux toward downstream 2-PE/tyrosol pathway, the relevant genes of three rate limiting steps including aroF, aroB and aroL were subcloned and overexpressed from plasmid. Upon simple batch cultivation, these strains separately yielded 369 ± 25 mg l-1 2-PE and 437 ± 33 mg l-1 tyrosol from 4.5 ± 0.21 g l-1 glucose. Final titer in the shake flask was further improved through glucose fed-batch fermentation to 1.75 ± 0.12 g l-1 2-PE and 1.68 ± 0.19 g l-1 tyrosol. The subsequent significant enhancement of 2-PE/tyrosol production occurred through employing in situ product removal (ISPR) techniques including two-phase extraction by different organic compounds (Etschmann et al. 2002; Rüffer et al. 2004; Schügerl and Hubbuch 2005; Hu and Xu 2011; Chreptowicz et al. 2018). In subsequent glucose-limited fed-batch cultivation with a benchtop bioreactor system (0.75 l), a final 2-PE and tyrosol-titer of 3.1 g l-1 and 3.6 g l-1 reached with a yield and a space-time-yield of 0.07 g g-1 and 0.03 g l-1 h-1 for 2-PE and 0.08 g g-1 and 0.04 g l-1 h-1 for tyrosol, respectively. These works have successfully demonstrated the possibility of synthesizing of several invaluable fine chemicals in whole-cell system using plasmid based-E.coli strains. In addition, the titter and yield previously reported in the biosynthesis of aromatic amines (L-PAPA, PAPE or 4-APA) or even aromatic alcohols (2-PE or tyrosol) have been significantly improved in this study.Aromatische Amine (AA) sind eine wichtige Gruppe von Industriechemikalien, die für viele technische und pharmazeutische Anwendungen genutzt werden. Diese können als Bausteine für die Herstellung von Medikamenten (Bedair et al. 2006; Jobdevairakkam und Velladurai 2009; Sacco und Bientinesi 2016), Antibiotika, Kunststoffen und aromatischen Polymeren genutzt werden (Arora 2015; Masuo et al., 2016; Tsuge et al . 2016; Kawasaki et al. 2018). Darüber hinaus werden aromatische Alkohole; in Parfums, Kosmetika, Nahrungsmitteln und Pharmazeutika verwendet (Etschmann et al. 2002; Miró-Casas et al. 2003; Bai et al. 2014). Die meisten AA und aromatischen Alkohole werden chemisch aus erdölbasierten Rohstoffen synthetisiert. Diese AA sind ungünstig für die Herstellung von Kosmetika, Arzneimitteln oder Nahrungsmittelbestandteilen. Daher ist eine natürliche mikrobielle Biosynthese dieser wertvollen Verbindungen mit E. coli ein attraktiver Ansatz. Im ersten Teil dieser Arbeit wurde ein De-novo-Biosyntheseweg für die Produktion von drei aromatischen Aminen, para-Aminophenylalanin (L-PAPA), para-Aminophenylethanol (PAPE) und 4-Aminophenylessigsäure (4-APA) aus Glukose/Glyzerin durch genetische Modifikation in rekombinanten E. coli etabliert (Mohammadi et al. 2018 and 2019). Zur Erzeugung eines Plattformstamms für die L-PAPA-Produktion wurden die Gene pabAB aus Corynebacterium glutamicum (Kozak 2006; Stolz et al. 2007), papB und papC aus Streptomyces venezuelae (Blanc et al. 1997; He et al. 2001; Mehl et al. 2003) in E. coli FUS4.7R heterolog mittels Plasmiden überexprimiert (Gottlieb et al. 2014). In E. coli FUS4BCR wurde anschließend der metabolische Fluss durch Überexpression der Phenylpyruvat-Decarboxylase (aro10) aus Saccharomyces cerevisiae (Vuralhan et al. 2003 und 2005; Kneen et al. 2011) oder durch aro10 mit feaB (Phenylacetaldehyd-Dehydrogenase) zur Produktion von PAPE und 4-APA optimiert. Die gentechnisch veränderten E. coli-Stämme wurden in Schüttelkolben mit Fed-Batch-Bedingungen kultiviert und mittels HPLC und LC-MS auf l-PAPA, PAPE und 4-APA-Produktion untersucht. In den einfachen Schüttelkolben-Experimenten erzeugte der l-PAPA produzierende Stamm 0,534 ± 0,024 g l-1 l-PAPA aus 5 ± 0,24 g l-1 Glyzerin. Außerdem führte die zusätzliche Einführung von aro10 und yahK (Aldehyd-Reduktase) in den l-PAPA-produzierenden Stamm zu 0,526 ± 0,025 g l-1 PAPE. Darüber hinaus wurde durch die Überexpression von feaB in den PAPE-produzierenden Stamm ein Titer von 0,458 ± 0,014 g l-1 4-APA ermöglicht. Schließlich wurde durch weitere Stammverbesserungen und Optimierungen der Wachstumsbedingungen mit Glukose/Glyzerol- Zufütterung der Titer von l-PAPA, PAPE und 4-APA auf etwa 5,5 ± 0,4 g l-1, 2,5 ± 0,15 g l-1 und 3,4 ± 0,3 g l-1 erhöht. Bei anschließender Fed-Batch-Kultivierung mit einem Endvolumen von 12,2 L mit Glyzerin als Kohlenstoffquelle wurde ein End-Titer von 16,7 g l-1 l-PAPA erhalten. Dies entspricht einer Ausbeute von 0,13 l-PAPA / Glycerin (g g-1) und einer Raum-Zeit-Ausbeute von 0,22 g l-1 h-1 l-PAPA über den gesamten Prozess. Darüber hinaus wurde ein De-novo Biosyntheseweg für die Produktion von 2-Phenylethanol (2-PE)/Tyrosol aus Glucose mit gentechnisch veränderten E. coli-Stämmen basierend auf der Plasmidexpression konstruiert. Ausgehend von Chorismat, dem direkten Vorläufer von Phenylpyruvat (PP)/ 4-Hydroxyphenylpyruvat (4-HPP), wurde ein künstlicher Ehrlich-Biosyntheseweg in Richtung 2-PE oder Tyrosol generiert (Etschmann et al. 2002). Um einen Plattformstamm für die Produktion von 2-PE und Tyrosol aus dem Shikimatweg zu erzeugen, wurde die Gene pheA oder tyrA kodierende Proteine Chorismatmutase/Prephenatdehydratase oder Prephenatdehydrogenase (Rüffer et al. 2004; Gottlieb et al. 2014 ) zusätzlich in E. coli überexprimiert. Im nächsten Schritt wurde der metabolische Fluss durch die Überexpression von aro10 in die 2-PE- und Tyrosol-Produktion gelenkt. Um den Fluss in Richtung des stromaufwärts gelegenen 2-PE/Tyrosol-weges zu erhöhen, wurden die relevanten Gene der drei geschwindigkeitsbegrenzenden Schritte im Shikimatweg aroF, aroB und aroL, überexprimiert. Nach Batch-Kultivierung ergaben diese Stämme 369 ± 25 mg l-1 2-PE und 437 ± 33 mg l-1 Tyrosol aus 4,5 ± 0,21 g l-1 Glukose. Der Endtiter im Schüttelkolben wurde durch eine Glukose-Fed-Batch-Fermentation auf 1,75 ± 0,12 g l-1 2-PE und 1,68 ± 0,19 g l-1 Tyrosol erhöht. Eine anschließende signifikante Steigerung der 2-PE / Tyrosol-Produktion erfolgte durch Anwendung eines In-situ-Verfahrens zur Produktentfernung (ISPR). Diese Zweiphasenextraktion wurde mit verschiedenen organischen Verbindungen untersucht (Etschmann et 2002; Schügerl und Hubbuch 2005; Astumi et al. 2008; Hu und Xu 2011). In einer anschließenden Glucose-limitierten Fed-Batch-Kultivierung in einem Benchtop-Bioreaktorsystem (0,75 l) wurde ein Endtiter von 3,1 g l-1 2-PE und 3,6 g l-1 Tyrosol mit einer Ausbeute und einem Raum-Zeit-Verhältnis von 0,07 g g-1 und 0,03 g 1-1 h-1 für 2-PE bzw. 0,08 g g-1 bzw. 0,04 g l-1 h-1 für Tyrosol erreicht. Diese Arbeit zeigt, dass die Synthese (im Gramm-Maßstab) von aromatischen Aminen (bzw. l-PAPA, PAPE oder 4-APA) und aromatischen Alkoholen (bzw. 2-PE oder Tyrosol) mit rekombinanten E. coli Stämmen möglich ist

بررسی مقایسه‌ای مهارت‌های نحوی کودکان کم‌شنوا و شنوای فارسی زبان پیش دبستانی

مقدمه: بررسی مهارت‌هاي نحوي کودکان آسيب ديده شنوايي از حوزه‌هاي مورد توجه آسيب‌شناسان گفتار و زبان است. در اين مطالعه     ميانگين طول گفته، نوع و تعداد الگوهاي خطاي گفتار كودكان كم‌شنوا در دو نوع نمونه گفتار ( آزاد و توصيفي) با همتايان شنوايشان مقايسه شد. مواد و روش‌ها: در این پژوهش مقطعی- توصیفی- تحلیلی، 16 کودک شنوا و 9 کودک کم‌شنوای 48 تا 72 ماهه تک زبانه و فارسی زبان از دو مرکز توان‌بخشی و مهدهای کودک شهر تهران به روش نمونه‌گیری در دسترس انتخاب شدند. داده‌های گفتار توصیفی با روش بازگویی داستان و توصیف تصویر و داده‌های گفتار آزاد از طریق پرسش‌های مکمل جمع‌آوری شد. تحلیل زبانی داده‌های جمع‌آوری شده، به دو روش كمي و كيفي مبتني بر صداي ضبط شده صورت پذيرفت. تحلیل آماری داده‌هاي به دست آمده با استفاده از آزمون‌هاي پارامتريك و غیر پارامتريك و Mann-Whitney U و t انجام شد. يافته‌ها: تحلیل داده‌هاي زباني بین دو گروه کم‌شنوا و شنوا حاكي از تفاوت معنی‌دار میانگین طول گفته (MLU) بر حسب تکواژ در هر دو نوع گفتار آزاد و توصیفی بوده (به ترتیب 002/0 = P و 001/0 > P). مقایسه میانگین كل خطاها هم در گفتار آزاد و هم در گفتار توصيفي بین دو گروه تفاوت معنی‌داری نشان داد (به ترتیب 003/0 = P و 001/0 > P). در گفتار توصیفی کودکان کم‌شنوا بیشترین خطای دستوری حذف نادرست و در کودکان شنوا انتخاب نابجا بود (به ترتیب 5/48 درصد و 2/38 درصد) و در گفتار آزاد بیشترین خطای هر دو گروه شنوا و کم‌شنوا حذف نابجای دستوری بود (به ترتیب 4/47 درصد و 8/38 درصد). نتیجه‌گیری: در مطالعه بين گروهي کودکان کم‌شنوا علاوه بر MLU کوتاه‌تر به وي‍‍ژه در گفتار آزاد نسبت به شنواها از نظر داشتن نوع خطاهای صرفی و نحوی نیز با آنان تفاوت معنی‌داری نشان دادند. کلید واژه‌ها: زبان فارسي، كودكان، کم‌شنوايي، میانگین طول گفته، مهارت‌های نحوی 

A New Hybrid Multi-Objective Scheduling Model for Hierarchical Hub and Flexible Flow Shop Problems

Technologies and lifestyles have been increasingly geared toward consumerism in recent years. Accordingly, it is both the price and the delivery time that matter most to the ultimate customers of commercial enterprises. Consequently, the importance of having an optimal delivery time is becoming increasingly evident these days. Scheduling can be used to optimize supply chains and production systems in this manner, which is one practical method for lowering costs and boosting productivity. This paper suggests a multi-objective scheduling model for hierarchical hub structures (HHS) with three levels of service. The factory and customers hub (second level) and central are on the first level in which the factory has a Flexible Flow Shop (FFS) environment. The noncentral hub (third level) is responsible for the delivery of products made in the factory to customers. Customer nodes and factories are connected separately to the second level, and the non-central hubs are connected to the third level. The model's objective is to minimize transportation and production costs and product arrival times. To validate and evaluate the model, small instances have been solved and analyzed in detail with the weighted sum and e-constraint methods. Consequently, based on the ideal mean distance (MID) metric, the two methods were compared for the designed instances. As NP-hardness causes the previously proposed methods to solve large-scale problems to be time-consuming, a meta-heuristic method was developed to solve the large-scale problem