Search results for: DNA synthesis

Authors: O. Gsib, U. Peirera, C. Egles, S. A. Bencherif

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In skin regenerative medicine, one of the critical issues is to produce a three-dimensional scaffold with optimized porosity for dermal fibroblast infiltration and neovascularization, which exhibits high mechanical properties and displays sufficient wound healing characteristics. In this study, we report on the synthesis and characterization of macroporous sequential interpenetrating polymer networks (IPNs) combining skin wound healing properties of fibrin with the excellent physical properties of polyethylene glycol (PEG). Fibrin fibers serve as a provisional biologically active network to promote cell adhesion and proliferation while PEG provides the mechanical stability to maintain the entire 3D construct. After having modified both PEG and Serum Albumin (used for promoting enzymatic degradability) by adding methacrylate residues (PEGDM and SAM, respectively), Fibrin/PEGDM-SAM sequential IPNs were synthesized as follows: Macroporous sponges were first produced from PEGDM-SAM hydrogels by a freeze-drying technique and then rehydrated by adding the fibrin precursors. Environmental Scanning Electron Microscopy (ESEM) and Confocal Laser Scanning Microscopy (CLSM) were used to characterize their microstructure. Human dermal fibroblasts were cultivated during one week in the constructs and different cell culture parameters (viability, morphology, proliferation) were evaluated. Subcutaneous implantations of the scaffolds were conducted on five-week old male nude mice to investigate their biocompatibility in vivo. We successfully synthesized interconnected and macroporous Fibrin/PEGDM-SAM sequential IPNs. The viability of primary dermal fibroblasts was well maintained (above 90%) after 2 days of culture. Cells were able to adhere, spread and proliferate in the scaffolds suggesting the suitable porosity and intrinsic biologic properties of the constructs. The fibrin network adopted a spider web shape that covered partially the pores allowing easier cell infiltration into the macroporous structure. To further characterize the in vitro cell behavior, cell proliferation (EdU incorporation, MTS assay) is being studied. Preliminary histological analysis of animal studies indicated the persistence of hydrogels even after one-month post implantation and confirmed the absence of inflammation response, good biocompatibility and biointegration of our scaffolds within the surrounding tissues. These results suggest that our Fibrin/PEGDM-SAM IPNs could be considered as potential candidates for dermis regenerative medicine. Histological analysis will be completed to further assess scaffold remodeling including de novo extracellular matrix protein synthesis and early stage angiogenesis analysis. Compression measurements will be conducted to investigate the mechanical properties.

Keywords: fibrin, hydrogels for dermal reconstruction, polyethylene glycol, semi-interpenetrating polymer network

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Authors: Takahiro Saida, Takahiro Kogiso, Takahiro Maruyama

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The ordered structural carbon (OSC) material is expected to apply to the electrode of secondary batteries, the catalyst supports, and the biomaterials because it shows the low substance-diffusion resistance by its uniform pore size. In general, the OSC material is synthesized using the template material. Changing size and shape of this template provides the pore size of OSC material according to the purpose. Depositing the oxide nanosheets on the polymer sphere template by the layer by layer (LbL) method was reported as one of the preparation methods of OSC material. The LbL method can provide the controlling thickness of structural wall without the surface modification. When the preparation of the uniform carbon sphere prepared by the LbL method which composed of the graphene oxide wall and the polymethyl-methacrylate (PMMA) core, the reduction treatment will be the important object. Since the graphene oxide has poor electron conductivity due to forming a lot of functional groups on the surface, it could be hard to apply to the electrode of secondary batteries and the catalyst support of fuel cells. In this study, the graphene oxide wall of carbon sphere was reduced by the thermal treatment under the vacuum conditions, and its crystalline structure and electronic state were characterized. Scanning electron microscope images of the carbon sphere after the heat treatment at 300ºC showed maintaining sphere shape, but its shape was collapsed with increasing the heating temperature. In this time, the dissolution rate of PMMA core and the reduction rate of graphene oxide were proportionate to heating temperature. In contrast, extending the heating time was conducive to the conservation of the sphere shape. From results of X-ray photoelectron spectroscopy analysis, its electronic state of the surface was indicated mainly sp² carbon. From the above results, we succeeded in the synthesis of the sphere structure composed by the reduction graphene oxide.

Keywords: carbon sphere, graphene oxide, reduction, layer by layer

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Authors: Nhan N. T. Ton, Anh T. N. Dao, Kouichirou Katou, Toshiaki Taniike

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Facile electron-hole recombination and the broad band gap are two major drawbacks of titanium dioxide (TiO₂) when applied in visible-light photocatalysis. Hybridization of TiO₂ with graphene is a promising strategy to lessen these pitfalls. Recently, there have been many reports on the synthesis of TiO₂/graphene nanocomposites, in most of which graphene oxide (GO) was used as a starting material. However, the reduction of GO introduced a large number of defects on the graphene framework. In addition, the sensitivity of titanium alkoxide to water (GO usually contains) significantly obstructs the uniform and controlled growth of TiO₂ on graphene. Here, we demonstrate a novel technique to synthesize TiO₂/graphene nanocomposites without the use of GO. Graphene dispersion was obtained through the chemical exfoliation of graphite in titanium tetra-n-butoxide with the aid of ultrasonication. The dispersion was directly used for the sol-gel reaction in the presence of different catalysts. A TiO₂/reduced graphene oxide (TiO₂/rGO) nanocomposite, which was prepared by a solvothermal method from GO, and the commercial TiO₂-P25 were used as references. It was found that titanium alkoxide afforded the graphene dispersion of a high quality in terms of a trace amount of defects and a few layers of dispersed graphene. Moreover, the sol-gel reaction from this dispersion led to TiO₂/graphene nanocomposites featured with promising characteristics for visible-light photocatalysts including: (I) the formation of a TiO₂ nano layer (thickness ranging from 1 nm to 5 nm) that uniformly and thinly covered graphene sheets, (II) a trace amount of defects on the graphene framework (low ID/IG ratio: 0.21), (III) a significant extension of the absorption edge into the visible light region (a remarkable extension of the absorption edge to 578 nm beside the usual edge at 360 nm), and (IV) a dramatic suppression of electron-hole recombination (the lowest photoluminescence intensity compared to reference samples). These advantages were successfully demonstrated in the photocatalytic decomposition of methylene blue under visible light irradiation. The TiO₂/graphene nanocomposites exhibited 15 and 5 times higher activity than TiO₂-P25 and the TiO₂/rGO nanocomposite, respectively.

Keywords: chemical exfoliation, photocatalyst, TiO₂/graphene, sol-gel reaction

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Authors: Neelma Ashraf

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Actinomycetes, particularly genus Streptomyces is of great importance due to their role in the discovery of new natural products, particularly antimicrobial secondary metabolites in the medicinal science and biotechnology industry. Different Streptomyces strains were isolated from Helianthus annuus plants and tested for antibacterial and antifungal activities. The most promising five strains were chosen for further investigation, and growth conditions for antibiotic synthesis were optimised. The supernatants were extracted in different solvents, and the extracted products were analyzed using liquid chromatography-mass spectrometry (LC-MS) and biological testing. From one of the potent strains Streptomyces globusus sp. BR123, a compound lavendamycin was identified using these analytical techniques. In addition, this potent strain also produces a strong antifungal polyene compound with a quasimolecular ion of 2072. Streptomyces sp. BR123 was genome sequenced because of its promising antimicrobial potential in order to identify the gene cluster responsible for analyzed compound “lavendamycin”. The genome analysis yielded candidate genes responsible for the production of this potent compound. The genome sequence of 8.15 Mb of Streptomyces sp. isolate BR123 with a GC content of 72.63% and 8103 protein coding genes was attained. Many antimicrobial, antiparasitic, and anticancerous compounds were detected through multiple biosynthetic gene clusters predicted by in-Silico analysis. Though, the novelty of metabolites was determined through the insignificant resemblance with known biosynthetic gene clusters. The current study gives insight into the bioactive potential of Streptomyces sp. isolate BR123 with respect to the synthesis of bioactive secondary metabolites through genomic and spectrometric analysis. Moreover, the comparative genome study revealed the connection of isolate BR123 with other Streptomyces strains, which could expand the knowledge of this genus and the mechanism involved in the discovery of new antimicrobial metabolites.

Keywords: streptomyces, secondary metabolites, genome, biosynthetic gene clusters, high performance liquid chromatography, mass spectrometry

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Authors: V. S. Bushkova

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It is well known that in recent years magnetic materials have received increased attention due to their properties. For this reason a significant number of patents that were published during the last decade are oriented towards synthesis and study of such materials. The aim of this work is to create and study ferrite nanocrystalline materials with spinel structure, using sol-gel technology with participation of auto-combustion. This method is perspective in that it is a cheap and low-temperature technique that allows for the fine control on the product’s chemical composition.

Keywords: magnetic materials, ferrites, sol-gel technology, nanocrystalline powders

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Authors: Mohsin Ejaz, Shiao-Wei Kuo

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The growing production and exploitation of fossil fuels have placed human society in serious environmental issues. As a result, it's critical to design efficient and eco-friendly energy production and storage techniques. Porous organic polymers (POPs) are multi-dimensional porous network materials developed through the formation of covalent bonds between different organic building blocks that possess distinct geometries and topologies. POPs have tunable porosities and high surface area making them a good candidate for an effective electrode material in energy storage applications. Herein, we prepared a fully benzoxazine-based porous organic polymers (TPA–DHTP–BZ POP) through sonogashira coupling of dihydroxyterephthalaldehyde (DHPT) and triphenylamine (TPA) containing benzoxazine (BZ) monomers. Firstly, both BZ monomers (TPA-BZ-Br and DHTP-BZ-Ea) were synthesized by three steps, including Schiff base, reduction, and mannich condensation reaction. Finally, the TPA–DHTP–BZ POP was prepared through the sonogashira coupling reaction of brominated monomer (TPA-BZ-Br) and ethynyl monomer (DHTP-BZ-Ea). Fourier transform infrared (FTIR) and solid-state nuclear magnetic resonance (NMR) spectroscopy confirmed the successful synthesis of monomers as well as POP. The porosity of TPA–DHTP–BZ POP was investigated by the N₂ absorption technique and showed a Brunauer–Emmett–Teller (BET) surface area of 196 m² g−¹, pore size 2.13 nm and pore volume of 0.54 cm³ g−¹, respectively. The TPA–DHTP–BZ POP experienced thermal ring-opening polymerization, resulting in poly (TPA–DHTP–BZ) POP having strong inter and intramolecular hydrogen bonds formed by phenolic groups and Mannich bridges, thereby enhancing CO₂ capture and supercapacitive performance. The poly(TPA–DHTP–BZ) POP demonstrated a remarkable CO₂ capture of 3.28 mmol g−¹ and a specific capacitance of 67 F g−¹ at 0.5 A g−¹. Thus, poly(TPA–DHTP–BZ) POP could potentially be used for energy storage and CO₂ capture applications.

Keywords: porous organic polymer, benzoxazine, sonogashira coupling, CO₂, supercapacitor

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Authors: Cameron Wilson, Megan Hanrahan, Katie Brittain, Riona McArdle, Alison Keogh, Lynn Rochester

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Background: The loss of mobility and functional dependence is a significant marker in the progression of neurodegenerative diseases such as Parkinson’s Disease (PD). Pharmacological, surgical, and therapeutic treatments are available that can help in the management and amelioration of PD symptoms; however, these only prolong more severe symptoms. Accordingly, ensuring people with PD can maintain independence and a healthy wellbeing are essential in establishing an effective treatment option for those afflicted. Existing literature reviews have examined experiences in engaging with PD treatment options and the impact of PD on independence and wellbeing. Although, the literature fails to explore the influence of treatment options on independence and wellbeing and therefore misses what people value in their treatment. This review is the first that synthesises the impact of mobility-related treatments on independence and wellbeing in people with PD and their carers, offering recommendations to clinical practice and provides a conceptual framework (in development) for future research and practice. Objectives: To explore the impact of mobility-related treatment (both pharmacological and non-pharmacological) on the independence and wellbeing of people with PD and their carers. To propose a conceptual framework to patients, carers and clinicians which captures the qualities people with PD value as part of their treatment. Methods: We performed a critical interpretive synthesis of qualitative evidence, searching six databases for reports that explored the impact of mobility-related treatments (both drug and non-pharmacological) on independence and wellbeing in Parkinson’s Disease. The types of treatments included medication (Levodopa and Amantadine), dance classes, Deep-Brain Stimulation, aquatic therapies, physical rehabilitation, balance training and foetal transplantation. Data was extracted, and quality was assessed using an adapted version of the NICE Quality Appraisal Tool Appendix H before being synthesised according to the critical interpretive synthesis framework and meta-ethnography process. Results: From 2301 records, 28 were eligible. Experiences and impact of treatment pathway on independence and wellbeing was similar across all types of treatments and are described by five inter-related themes: (i) desire to maintain independence, (ii) treatment as a social experience during and after, (iii) medication to strengthen emotional health, (iv) recognising physical capacity and (v) emphasising the personal journey of Parkinson’s treatments. Conclusion: There is a complex and inter-related experience and effect of PD treatments common across all types of treatment. The proposed conceptual framework (in development) provides patients, carers, and clinicians recommendations to personalise the delivery of PD treatment, thereby potentially improving adherence and effectiveness. This work is vital to disseminate as PD treatment transitions from subjective and clinically captured assessments to a more personalised process supplemented using wearable technology.

Keywords: parkinson's disease, medication, treatment, dance, review, healthcare, delivery, levodopa, social, emotional, psychological, personalised healthcare

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Authors: Rama Devi Kyatham, D. Ashok, K. S. K. Rao Patnaik, Raju Bathula

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We have shown the importance of pyrazoles as anti-microbial chemical entities. These compounds have generally been considered significant due to their wide range of pharmacological acivities and their discovery motivates new avenues of research.The proposed pyrazoles were synthesized and evaluated for their anti-microbial activities. The Synthesized compounds were analyzed by different spectroscopic methods.

Keywords: pyrazoles, validation, resistant microbial strains, anti-microbial activities

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Authors: Bozena Tyliszczak, Anna Drabczyk, Sonia Kudlacik-Kramarczyk, Agnieszka Sobczak-Kupiec

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Introduction: Nanomaterials become one of the leading materials in the synthesis of various compounds. This is a reason for the fact that nano-size materials exhibit other properties compared to their macroscopic equivalents. Such a change in size is reflected in a change in optical, electric or mechanical properties. Among nanomaterials, particular attention is currently directed into gold nanoparticles. They find application in a wide range of areas including cosmetology or pharmacy. Additionally, nanogold may be a component of modern wound dressings, which antibacterial activity is beneficial in the viewpoint of the wound healing process. Specific properties of this type of nanomaterials result in the fact that they may also be applied in cancer treatment. Studies on the development of new techniques of the delivery of drugs are currently an important research subject of many scientists. This is due to the fact that along with the development of such fields of science as medicine or pharmacy, the need for better and more effective methods of administering drugs is constantly growing. The solution may be the use of drug carriers. These are materials that combine with the active substance and lead it directly to the desired place. A role of such a carrier may be played by gold nanoparticles that are able to covalently bond with many organic substances. This allows the combination of nanoparticles with active substances. Therefore gold nanoparticles are widely used in the preparation of nanocomposites that may be used for medical purposes with special emphasis on drug delivery. Methodology: As part of the presented research, synthesis of composites was carried out. The mentioned composites consisted of the polymer matrix and gold nanoparticles that were introduced into the polymer network. The synthesis was conducted with the use of a crosslinking agent, and photoinitiator and the materials were obtained by means of the photopolymerization process. Next, incubation studies were conducted using selected liquids that simulated fluids are occurring in the human body. The study allows determining the biocompatibility of the tested composites in relation to selected environments. Next, the chemical structure of the composites was characterized as well as their sorption properties. Conclusions: Conducted research allowed for the preliminary characterization of prepared polymer composites containing gold nanoparticles in the viewpoint of their application for biomedical use. Tested materials were characterized by biocompatibility in tested environments. What is more, synthesized composites exhibited relatively high swelling capacity that is essential in the viewpoint of their potential application as drug carriers. During such an application, composite swells and at the same time releases from its interior introduced active substance; therefore, it is important to check the swelling ability of such material. Acknowledgements: The authors would like to thank The National Science Centre (Grant no: UMO - 2016/21/D/ST8/01697) for providing financial support to this project. This paper is based upon work from COST Action (CA18113), supported by COST (European Cooperation in Science and Technology).

Keywords: nanocomposites, gold nanoparticles, drug carriers, swelling properties

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Authors: María José Carrero, Ana M. Borreguero, Juan F. Rodríguez, María M. Velencoso, Ángel Serrano, María Jesús Ramos

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Flame-retardants are incorporated in different materials in order to reduce the risk of fire, either by providing increased resistance to ignition, or by acting to slow down combustion and thereby delay the spread of flames. In this work, polyether polyols with fire retardant properties were synthesized due to their wide application in the polyurethanes formulation. The combustion of polyurethanes is primarily dependent on the thermal properties of the polymer, the presence of impurities and formulation residue in the polymer as well as the supply of oxygen. There are many types of flame retardants, most of them are phosphorous compounds of different nature and functionality. The addition of these compounds is the most common method for the incorporation of flame retardant properties. The employment of glycerol phosphate sodium salt as initiator for the polyol synthesis allows obtaining polyols with phosphate groups in their structure. However, some of the critical points of the use of glycerol phosphate salt are: the lower reactivity of the salt and the necessity of a solvent (dimethyl sulfoxide, DMSO). Thus, the main aim in the present work was to determine the amount of the solvent needed to get a good solubility of the initiator salt. Although the anionic polymerization mechanism of polyether formation is well known, it seems convenient to clarify the role that DMSO plays at the starting point of the polymerization process. Regarding the fact that the catalyst deprotonizes the hydroxyl groups of the initiator and as a result of this, two water molecules and glycerol phosphate alkoxide are formed. This alkoxide, together with DMSO, has to form a homogeneous mixture where the initiator (solid) and the propylene oxide (PO) are soluble enough to mutually interact. The addition rate of PO increased when the solvent/initiator ratios studied were increased, observing that it also made the initiation step shorter. Furthermore, the molecular weight of the polyol decreased when higher solvent/initiator ratios were used, what revealed that more amount of salt was activated, initiating more chains of lower length but allowing to react more phosphate molecules and to increase the percentage of phosphorous in the final polyol. However, the final phosphorous content was lower than the theoretical one because only a percentage of salt was activated. On the other hand, glycerol phosphate disodium salt was still partially insoluble in DMSO studied proportions, thus, the recovery and reuse of this part of the salt for the synthesis of new flame retardant polyols was evaluated. In the recovered salt case, the rate of addition of PO remained the same than in the commercial salt but a shorter induction period was observed, this is because the recovered salt presents a higher amount of deprotonated hydroxyl groups. Besides, according to molecular weight, polydispersity index, FT-IR spectrum and thermal stability, there were no differences between both synthesized polyols. Thus, it is possible to use the recovered glycerol phosphate disodium salt in the same way that the commercial one.

Keywords: DMSO, fire retardants, glycerol phosphate disodium salt, recovered initiator, solvent

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Authors: Mohamed dammak

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Great attention has been paid to the design and synthesis of novel organic-inorganic compounds in recent decades because of their structural variety and the large diversity of atomic arrangements. In this work, the structure for the novel dimethyl aminopyridine tetrachlorocobaltate (C₇H₁₁N₂)₂CoCl₄ prepared by the slow evaporation method at room temperature has been successfully discussed. The X-ray diffraction results indicate that the hybrid material has a triclinic structure with a P space group and features a 0D structure containing isolated distorted [CoCl₄]2- tetrahedra interposed between [C7H11N²⁻]+ cations forming planes perpendicular to the c axis at z = 0 and z = ½. The effect of the synthesis conditions and the reactants used, the interactions between the cationic planes, and the isolated [CoCl4]2- tetrahedra are employing N-H...Cl and C-H…Cl hydrogen bonding contacts. The inspection of the Hirshfeld surface analysis helps to discuss the strength of hydrogen bonds and to quantify the inter-contacts. A phase transition was discovered by thermal analysis at 390 K, and comprehensive dielectric research was reported, showing a good agreement with thermal data. Impedance spectroscopy measurements were used to study the electrical and dielectric characteristics over a wide range of frequencies and temperatures, 40 Hz–10 MHz and 313–483 K, respectively. The Nyquist plot (Z" versus Z') from the complex impedance spectrum revealed semicircular arcs described by a Cole-Cole model. An electrical circuit consisting of a link of grain and grain boundary elements is employed. The real and imaginary parts of dielectric permittivity, as well as tg(δ) of (C₇H₁₁N₂)₂CoCl₄ at different frequencies, reveal a distribution of relaxation times. The presence of grain and grain boundaries is confirmed by the modulus investigations. Electric and dielectric analyses highlight the good protonic conduction of this material.

Keywords: organic-inorganic, phase transitions, complex impedance, protonic conduction, dielectric analysis

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Authors: Samuel Abebe Ebebo

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Scale precipitation causes a major issue for geothermal power plants because it reduces the production rate of geothermal energy. Each geothermal power plant's different chemical and physical conditions can cause the scale to precipitate under a particular set of fluid-rock interactions. Depending on the mineral, it is possible to have scale in the production well, steam separators, heat exchangers, reinjection wells, and everywhere in between. The scale consists mainly of smectite and trace amounts of chlorite, magnetite, quartz, hematite, dolomite, aragonite, and amorphous silica. The smectite scale is one of the difficult scales at injection wells in geothermal power plants. X-ray diffraction and chemical composition identify this smectite as Stevensite. The characteristics and the scale of each injection well line are different depending on the fluid chemistry. The smectite scale has been widely distributed in pipelines and surface plants. Mineral water equilibrium showed that the main factors controlling the saturation indices of smectite increased pH and dissolved Mg concentration due to the precipitate on the equipment surface. This study aims to characterize the scales and geothermal fluids collected from the Onuma geothermal power plant in Akita Prefecture, Japan. Field tests were conducted on October 30–November 3, 2021, at Onuma to determine the pH control methods for preventing magnesium silicate scaling, and as exemplified, the formation of magnesium silicate hydrates (M-S-H) with MgO to SiO2 ratios of 1.0 and pH values of 10 for one day has been studied at 25 °C. As a result, M-S-H scale formation could be suppressed, and stevensite formation could also be suppressed when we can decrease the pH of the fluid by less than 8.1, 7.4, and 8 (at 97 °C) in the fluid from O-3Rb and O-6Rb, O-10Rg, and O-12R, respectively. In this context, the scales and fluids collected from injection wells at a geothermal power plant in Japan were analyzed and characterized to understand the formation conditions of Mg-silicate scales with on-site synthesis experiments. From the results of the characterizations and on-site synthesis experiments, the inhibition method of their scale formation is discussed based on geochemical modeling in this study.

Keywords: magnesium silicate, scaling, inhibitor, geothermal power plant

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Authors: Mohammed Sghir Taleb

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Forest ecosystems in Morocco are subject increasingly to natural and human pressures. Conscious of this problem, Morocco set a strategy that focuses on programs of in-situ and ex-situ biodiversity conservation. This study is the result of a synthesis of various existing studies on biodiversity and forest ecosystems. It gives an overview of Moroccan mountain forest ecosystems and flora diversity. It also focuses on the efforts made by Morocco to conserve and sustainably manage biodiversity.

Keywords: mountain, ecosystems, conservation, Morocco

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Authors: Chun-Fang Hsueh, Chen-Kang Chang

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Introduction: Branched-chain amino acids (BCAA) could reduce cerebral uptake of tryptophan, leading to decreased synthesis of serotonin in the brain. Arginine and citrulline could reduce exercise-induced hyperammonemia by increasing nitric oxide synthesis and the urea cycle. The combination of these supplements could reduce exercise-induced central fatigue. The purpose of this study was to examine the effect of BCAA, arginine, and citrulline supplementation on repeated swimming performance in teenage athletes. Methods: Eight male and eight female high school swimmers ingested 0.085 g/kg BCAA, 0.05 g/kg arginine and 0.05 g/kg citrulline (AA trial) or placebo (PL trial) in a randomized cross-over design. One hour after the ingestion, the subjects performed a 50 m sprint with their best style every 2 min for 8 times in an indoor 25 m pool. The subjects were asked to swim with their maximal effort each time. The time, stroke frequency and stroke length in each sprint were recorded. Venous blood samples were collected before and after the exercise. The time for each sprint was analyzed by 2-way analysis of variance with repeated measurement. Results: When all subjects were pooled together, total time for the AA trial was significantly faster than the PL trial (AA: 244.02 ± 22.94 s; PL: 247.55 ± 24.17 s, p < .001). Individual sprint time showed significant trial (p= .001) and trial x time (p= .004) effects. The post-hoc analysis revealed that the AA trial was significantly faster than the PL trial in the 2nd, 5th, and 6th sprint. In female subjects, there is a significant trial effect (p= .004) with the AA trial being faster in the 1st, 2nd, and 5th sprint. On the other hand, the trial effect was not significant (p= .072) in male subjects. Conclusions: The combined supplementation could improve 8 x 50 m performance in high school swimmers. The blood parameters including BCAA, tryptophan, NH₃, nitric oxide, and urea, as well as the stroke frequency and length in each sprint, are being analyzed. The results will be presented in the conference.

Keywords: central fatigue, hyperammonemia, tryptophan, urea

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Authors: Sutapa Mondal Roy, Suban K. Sahoo

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The primary aim of this work is to synthesis silver nanoparticles (AgNPs) through environmentally benign routes to avoid any chemical toxicity related undesired side effects. The nanoparticles were stabilized with drug ciprofloxacin (Cp) and were studied for their effectiveness as drug delivery agent. Targeted drug delivery improves the therapeutic potential of drugs at the diseased site as well as lowers the overall dose and undesired side effects. The small size of nanoparticles greatly facilitates the transport of active agents (drugs) across biological membranes and allows them to pass through the smallest capillaries in the body that are 5-6 μm in diameter, and can minimize possible undesired side effects. AgNPs are non-toxic, inert, stable, and has a high binding capacity and thus can be considered as biomaterials. AgNPs were synthesized from the nutrient broth supernatant after the culture of environment-friendly bacteria Bacillus subtilis. The AgNPs were found to show the surface plasmon resonance (SPR) band at 425 nm. The Cp capped Ag nanoparticles formation was complete within 30 minutes, which was confirmed from absorbance spectroscopy. Physico-chemical nature of the AgNPs-Cp system was confirmed by Dynamic Light Scattering (DLS), Transmission Electron Microscopy (TEM) etc. The AgNPs-Cp system size was found to be in the range of 30-40 nm. To monitor the kinetics of drug release from the surface of nanoparticles, the release of Cp was carried out by careful dialysis keeping AgNPs-Cp system inside the dialysis bag at pH 7.4 over time. The drug release was almost complete after 30 hrs. During the drug delivery process, to understand the AgNPs-Cp system in a better way, the sincere theoretical investigation is been performed employing Density Functional Theory. Electronic charge transfer, electron density, binding energy as well as thermodynamic properties like enthalpy, entropy, Gibbs free energy etc. has been predicted. The electronic and thermodynamic properties, governed by the AgNPs-Cp interactions, indicate that the formation of AgNPs-Cp system is exothermic i.e. thermodynamically favorable process. The binding energy and charge transfer analysis implies the optimum stability of the AgNPs-Cp system. Thus, the synthesized Cp-Ag nanoparticles can be effectively used for biological purposes due to its environmentally benign routes of synthesis procedures, which is clean, biocompatible, non-toxic, safe, cost-effective, sustainable and eco-friendly. The Cp-AgNPs as biomaterials can be successfully used for drug delivery procedures due to slow release of drug from nanoparticles over a considerable period of time. The kinetics of the drug release show that this drug-nanoparticle assembly can be effectively used as potential tools for therapeutic applications. The ease of synthetic procedure, lack of possible chemical toxicity and their biological activity along with excellent application as drug delivery agent will open up vista of using nanoparticles as effective and successful drug delivery agent to be used in modern days.

Keywords: silver nanoparticles, ciprofloxacin, density functional theory, drug delivery

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Authors: Malek Ali

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Composites materials of Poly (vinyl alcohol) (PVA)/Chitosan (CS) have been synthesized and characterized successfully. HNTs have been added to composites to enhance the mechanical and degradation properties by hydrogen bonding interactions, compatibility, and chemical crosslink between HNTs and PVA. PVA/CS/HNTs composites prepared with different concentration ratio. SEM micrographs of composites surface showed that more agglomeration with more chitosan ratio. Mechanical and degradation properties were characterized and the result indicates that Mechanical and degradation of 80%PVA/5%Chitosan/15%HNTs higher than the others PVA/CS/HNTs composites.

Keywords: PVA/chitosan, composites, PVA/CS/HNTs, HNTs

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Authors: Shalini Arora, Sri Sivakumar

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The deep removal of high molecular weight sulphur compounds (e.g., 4,6, dimethyl dibenzothiophene) is challenging due to their steric hindrance. Hydrogenation desulfurization (HYD) pathway is the main pathway to remove these sulfur compounds, and it is mainly governed by the number of type 2 sites. The formation of type 2 sites can be enhanced by modulating the pore structure and the interaction between the active metal and support. To this end, we report the enhanced HDS catalytic activity of ultrasmall NiMo supported on amorphous alumina (A-Al₂O₃) catalysts by one pot colloidal synthesis method followed by calcination and sulfidation. The amorphous alumina (A-Al₂O₃) was chosen as the support due to its lower surface energy, better physicochemical properties, and enhanced acidic sites (due to the dominance of tetra and penta coordinated [Al] sites) than crystalline alumina phase. At 20% metal oxide composition, NiMo supported on A-Al₂O₃ catalyst showed 1.4 and 1.2 times more reaction rate constant and turn over frequency (TOF) respectively than the conventional catalyst (wet impregnated NiMo catalysts) for HDS reaction of dibenzothiophene reactant molecule. A-Al₂O₃ supported catalysts represented enhanced type 2 sites formation (because this catalystpossesses higher sulfidation degree (80%) and NiMoS sites (19.3 x 10¹⁷ sites/mg) with desired optimum stacking degree (2.5) than wet impregnated catalyst at same metal oxide composition 20%) along with higher active metal dispersion, Mo edge site fraction. The experimental observations were also supported by DFT simulations. Lower heat of adsorption (< 4.2 ev for MoS2 interaction and < 3.15 ev for Ni doped MoS2 interaction) values for A-Al₂O₃ confirmed the presence of weaker metal-support interaction in A-Al₂O₃ in contrast to crystalline ℽ-Al₂O3. The weak metal-support interaction for prepared catalysts clearly suggests the higher formation of type 2 sites which leads to higher catalytic activity for HDS reaction.

Keywords: amorphous alumina, colloidal, desulfurization, metal-support interaction

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Authors: Masoumeh Ghorbania, Falk Liebnerb, Hendrikus W.G. van Herwijnenc, Johannes Konnertha

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Phenol formaldehyde (PF) resins are widely used as wood adhesives for variety of industrial products such as plywood, laminated veneer lumber and others. Lignin as a main constituent of wood has become well-known as a potential substitute for phenol in PF adhesives because of their structural similarity. During the last decades numerous research approaches have been carried out to substitute phenol with pulping-derived lignin, whereby the lower reactivity of resins synthesized with shares of lignin seem to be one of the major challenges. This work reports about a systematic screening of different types of lignin (plant origin and pulping process) for their suitability to replace phenol in phenolic resins. Lignin from different plant sources (softwood, hardwood and grass) were used, as these should differ significantly in their reactivity towards formaldehyde of their reactive phenolic core units. Additionally a possible influence of the pulping process was addressed by using the different types of lignin from soda, kraft, and organosolv process and various lignosulfonates (sodium, ammonium, calcium, magnesium). To determine the influence of lignin on the adhesive performance beside others the rate of viscosity development, bond strength development of varying hot pressing time and other thermal properties were investigated. To evaluate the performance of the cured end product, a few selected properties were studied at the example of solid wood-adhesive bond joints, compact panels and plywood. As main results it was found that lignin significantly accelerates the viscosity development in adhesive synthesis. Bonding strength development during curing of adhesives decelerated for all lignin types, while this trend was least for pine kraft lignin and spruce sodium lignosulfonate. However, the overall performance of the products prepared with the latter adhesives was able to fulfill main standard requirements, even after exposing the products to harsh environmental conditions. Thus, a potential application can be considered for processes where reactivity is less critical but adhesive cost and product performance is essential.

Keywords: phenol formaldehyde resin, lignin phenol formaldehyde resin, ABES, DSC

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Authors: Harriet Koshie Lamptey, Richard Boateng

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Mobile learning (m-learning) is a novel approach to knowledge acquisition and dissemination and is gaining global attention. Steady progress in wireless technologies and the portability of communication devices continue to broaden the scope and use of mobiles. With the convergence of Web functionality onto mobile platforms and the affordability and availability of mobile technology, m-learning has the potential of being the next prevalent channel of education in both formal and informal settings. There is substantive literature on developed countries but the state in developing countries (DCs) however appears vague. This paper is a synthesis of extant literature on mobile learning in DCs. The research interest is based on the fact that in DCs, mobile communication and internet connectivity are popular. However, its use in education is under explored. There are some reviews on the state, conceptualizations, trends and teacher education, but to the authors’ knowledge, no study has focused on mobile learning adoption and integration issues. This study examines issues and gaps associated with its adoption and integration in DCs higher education institutions. A qualitative build-up of literature was conducted using articles pooled from electronic databases (Google Scholar and ERIC). To enable criteria for inclusion and incorporate diverse study perspectives, search terms used were m-learning, DCs, higher education institutions, challenges, benefits, impact, gaps and issues. The synthesis revealed that though mobile technology has diffused globally, its pedagogical pursuit in DCs remains quite low. The absence of a mobile Web and the difficulty of resource conversion into mobile format due to lack of funding and technical competence is a stumbling block. Again, the lack of established design and implementation rules to guide the development of m-learning platforms in DCs is a hindrance. The absence of access restrictions on devices poses security threats to institutional systems. Negative perceptions that devices are taking over faculty roles lead to resistance in some situations. Resistance to change can be a hindrance to the acceptance and success of new systems. Lack of interest for m-learning is also attributed to lower technological literacy levels of the underprivileged masses. Scholarly works on m-learning in DCs is yet to mature. Most technological innovations are handed down from developed countries, and this constantly creates a lag for DCs. Lack of theoretical grounding was also identified which reduces the objectivity of study reports. The socio-cultural terrain of DCs results in societies with different views and needs that have been identified as a hindrance to research. Institutional commitment decisions, adequate funding for the necessary infrastructural development as well as multiple stakeholder participation is important for project success. Evidence suggests that while adoption decisions are readily made, successful integration of the concept for its full benefits to be realized is often neglected. Recommendations to findings were made to provide possible remedies to identified issues.

Keywords: developing countries, higher education institutions, mobile learning, literature review

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Authors: Julie Mariam Abraham, G. J. Melendez-Torres

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Background. Maternal mortality is disproportionately higher in low- and middle- income countries (LMICs) compared to other parts of the world. At the current pace of progress, the Sustainable Development Goals for maternal mortality rate will not be achieved by 2030. A variety of factors influence the increased risk of maternal complications in LMICs. These are exacerbated by socio-economic and political factors, including poverty, illiteracy, and gender inequality. This paper aims to use realist synthesis to identify the contexts, mechanisms, and outcomes (CMOs) of maternal health interventions conducted in LMICs to inform evidence-based practice for future maternal health interventions. Methods. In May 2022, we searched four electronic databases for systematic reviews of maternal health interventions in LMICs published in the last five years. We used open and axial coding of CMOs to develop an explanatory framework for intervention effectiveness. Results. After eligibility screening and full-text analysis, 44 papers were included. The intervention strategies and measured outcomes varied within reviews. Healthcare system level contextual factors were the most frequently reported, and infrastructural capacity was the most reported context. The most prevalent mechanism was increased knowledge and awareness. Discussion. Health system infrastructure must be considered in interventions to ensure effective implementation and sustainability. Healthcare-seeking behaviours are embedded within social and cultural norms, environmental conditions, family influences, and provider attitudes. Therefore, effective engagement with communities and families is important to create new norms surrounding pregnancy and delivery. Future research should explore community mobilisation and involvement to enable tailored interventions with optimal contextual fit.

Keywords: maternal mortality, service delivery and organisation, realist synthesis, sustainable development goals, overview of reviews

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Authors: Sh. Sohrabnezhad, A. Jafarzadeh

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In this paper, MCM-41 mesoporous material nanofibers were synthesized by an electrospinning technique. The nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), x-ray diffraction (XRD), and nitrogen adsorption–desorption measurement. Tetraethyl orthosilicate (TEOS) and polyvinyl alcohol (PVA) were used as a silica source and fiber forming source, respectively. TEM and SEM images showed synthesis of MCM-41 nanofibers with a diameter of 200 nm. The pore diameter and surface area of calcined MCM-41 nanofibers was 2.2 nm and 970 m²/g, respectively. The morphology of the MCM-41 nanofibers depended on spinning voltages.

Keywords: electrospinning, electron microscopy, fiber technology, porous materials, X-ray techniques

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Authors: Jitlada Chumee, Drenpen Seeburin

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The cellulose was extracted from pomelo peel and an etherification reaction used for converting cellulose to carboxymethyl cellulose (CMC). The pomelo peel was refluxed with 0.5 M HCl and 1 M NaOH solution at 90°C for 1 h and 2 h, respectively. The cellulose was bleached with calcium hypochlorite and used as precursor. The precursor was soaked in mixed solution between isopropyl alcohol and 40%w/v NaOH for 12 h. After that, chloroacetic acid was added and reacted at 55°C for 6 h. The optimum condition was 5 g of cellulose: 0.25 mole of NaOH : 0.07 mole of ClCH2COOH with 78.00% of yield. Moreover, the product had 0.54 of degree of substitution (DS).

Keywords: pomelo peel, carboxymethyl cellulose, bioplastic, extraction

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Authors: Flora Elvistia Firdaus

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The chemical structure of soybean oils have to be chemically modified through its tryglyceride to attain resemblance properties with petrochemicals. Sulfur acid catalyst in peracetic acid co-reagent has good performance on modified soybean oil strucutures through its unsaturated fatty acid moiety to the desired hydroxyl functional groups. A series of screening reactions have indicated that the ratio of acetic/peroxide acid 1:7.25 (mol/mol) with temperature of 600°C for soy-epoxide synthesis are prevailed for up-scaling of bodied soybean into 10 and 20 folds from initials. A two-step process was conducted for the preparation of soy-polyol in designated temperatures.

Keywords: soybean, polyol, up-scaling, polyurethane

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Authors: Evelyn Osehontue Uroro, Richard Bright, Jing Yang Quek, Krasimir Vasilev

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Bacterial infections have been a challenge both in the public and private sectors. The colonization of bacteria often occurs in medical devices such as catheters, heart valves, respirators, and orthopaedic implants. When biomedical devices are inserted into patients, the deposition of macromolecules such as fibrinogen and immunoglobin on their surfaces makes it easier for them to be prone to bacteria colonization leading to the formation of biofilms. The formation of biofilms on medical devices has led to a series of device-related infections which are usually difficult to eradicate and sometimes cause the death of patients. These infections require surgical replacements along with prolonged antibiotic therapy, which would incur additional health costs. It is, therefore, necessary to prevent device-related infections by inhibiting the formation of biofilms using intelligent technology. Antibiotic resistance of bacteria is also a major threat due to overuse. Different antimicrobial agents have been applied to microbial infections. They include conventional antibiotics like rifampicin. The use of conventional antibiotics like rifampicin has raised concerns as some have been found to have hepatic and nephrotoxic effects due to overuse. Hence, there is also a need for proper delivery of these antibiotics. Different techniques have been developed to encapsulate and slowly release antimicrobial agents, thus reducing host cytotoxicity. Examples of delivery systems are solid lipid nanoparticles, hydrogels, micelles, and polymeric nanoparticles. The different ways by which drugs are released from polymeric nanoparticles include diffusion-based release, elution-based release, and chemical/stimuli-responsive release. Polymeric nanoparticles have gained a lot of research interest as they are basically made from biodegradable polymers. An example of such a biodegradable polymer is polycaprolactone (PCL). PCL degrades slowly by hydrolysis but is often sensitive and responsive to stimuli like enzymes to release encapsulants for antimicrobial therapy. This study presents the synthesis of PCL nanoparticles loaded with rifampicin and the on-demand release of rifampicin for treating staphylococcus aureus infections.

Keywords: enzyme, Staphylococcus aureus, PCL, rifampicin

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Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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Authors: Mehmet Doğan, Mahir Alkan, Yasemin Turhan, Zürriye Gündüz, Pinar Beyli, Serap Doğan

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Advances and new discoveries in the field of the material science on the basis of technological developments have played an important role. Today, material science is branched the lower branches such as metals, nonmetals, chemicals, polymers. The polymeric nano composites have found a wide application field as one of the most important among these groups. Many polymers used in the different fields of the industry have been desired to improve the thermal stability. One of the ways to improve this property of the polymers is to form the nano composite products of them using different fillers. There are many using area of boron compounds and is increasing day by day. In order to the further increasing of the variety of using area of boron compounds and industrial importance, it is necessary to synthesis of nano-products and to find yourself new application areas of these products. In this study, PMMA/boronoxide nano composites were synthesized using solution intercalation, polymerization and melting methods; and PAA/boronoxide nano composites using solution intercalation method. Furthermore, rheological properties of nano composites synthesed according to melting method were also studied. Nano composites were characterized by XRD, FTIR-ATR, DTA/TG, BET, SEM, and TEM instruments. The effects of filler material amount, solvent types and mediating reagent on the thermal stability of polymers were investigated. In addition, the rheological properties of PMMA/boronoxide nano composites synthesized by melting method were investigated using High Pressure Capillary Rheometer. XRD analysis showed that boronoxide was dispersed in polymer matrix; FTIR-ATR that there were interactions with boronoxide between PAA and PMMA; and TEM that boronoxide particles had spherical structure, and dispersed in nano sized dimension in polymer matrix; the thermal stability of polymers was increased with the adding of boronoxide in polymer matrix; the decomposition mechanism of PAA was changed. From rheological measurements, it was found that PMMA and PMMA/boronoxide nano composites exhibited non-Newtonian, pseudo-plastic, shear thinning behavior under all experimental conditions.

Keywords: boronoxide, polymer, nanocomposite, rheology, characterization

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Authors: Héctor González Espinosa, Ricardo Ivan Cordova Chávez, Alejandra Contreras Ramos, Itzia Irene Padilla Martínez, José Guadalupe Trujillo Ferrara, Marvin Antonio Soriano Ursúa

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Boronic acids are able to create diester bonds with carbohydrates because of their hydroxyl groups; in nature, there are some organoborates with these characteristics, such as the calcium fructoborate, formed by the union of two fructose molecules and a boron atom, synthesized by plants. In addition, it has been observed that, in animal cells only the compounds with cis-diol functional groups are capable of linking to boric or boronic acids. The formation of these organoboron compounds could impair the physical and chemical properties of the precursors, even their acute toxicity. In this project, two carbohydrate-derived boron-containing compounds from D-fructose and D-arabinose and phenylboronic acid are analyzed by different spectroscopy techniques such as Raman, Infrared with Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR) and X-ray diffraction crystallography to describe their chemical characteristics. Also, an acute toxicity test was performed to determine their LD50 using the Lorke’s method. It was confirmed by multiple spectra the formation of the adducts by the generation of the diester bonds with a β-D-pyranose of fructose and arabinose. The most prominent findings were the presence of signals corresponding to the formation of new bonds, like the stretching of B-O bonds, or the absence of signals of functional groups like the hydroxyls presented in the reagents used for the synthesis of the adducts. The NMR spectra yielded information about the stereoselectivity in the synthesis reaction, observed by the interaction of the protons and their vicinal atoms in the anomeric and second position carbons; but also, the absence of a racemic mix by the finding of just one signal in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests by the Lorke’s method showed that the LD50 value for both compounds is 1265 mg/kg. Those results let us to propose these adducts as highly safe agents for further biological evaluation with medical purposes.

Keywords: acute toxicity, adduct, boron, carbohydrate, diester bond

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Authors: Vadim V. Zefirov, Victor E. Sizov, Marina A. Pigaleva, Igor V. Elmanovich, Mikhail S. Kondratenko, Marat O. Gallyamov

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This work presents a novel method for treating porous hydrophobic polyolefin membranes using supercritical carbon dioxide that allows usage of the modified membrane in redox flow batteries with an aqueous electrolyte. Polyolefin membranes are well known and widely used, however, they cannot be used as separators in redox flow batteries with an aqueous electrolyte since they have insufficient wettability, and therefore do not provide sufficient proton conductivity. The main aim of the presented work was the development of hydrophilic composites based on cheap membranes and precursors. Supercritical fluid was used as a medium for the deposition of the hydrophilic phase on the hydrophobic surface of the membrane. Due to the absence of negative capillary effects in a supercritical medium, a homogeneous composite is obtained as a result of synthesis. The in-situ synthesized silicon oxide nanoparticles and the chitosan polymer layer act as the hydrophilic phase and not only increase the affinity of the membrane towards the electrolyte, but also reduce the pore size of the polymer matrix, which positively affects the ion selectivity of the membrane. The composite material obtained as a result of synthesis has enhanced hydrophilic properties and is capable of providing proton conductivity in redox flow batteries. The morphology of the obtained composites was characterized by electron microscopy. To analyze the phase composition, infrared spectroscopy was used. The hydrophilic properties were studied by water contact angle measurements. In addition, the proton conductivity and ion selectivity of the obtained samples were studied, and tests in real redox flow batteries were performed. As a result, modified membrane was characterised in detail and moreover it was shown that modified cheap polyolefin membranes have pronounced proton conductivity and high ion selectivity, so their performance in a real redox flow battery approaches expensive commercial analogues, reaching 70% of energy efficiency.

Keywords: carbon dioxide, chitosan, polymer membrane, redox flow batteries, silica nanoparticles, supercritical fluid

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Authors: Nastaran Hazrati, Ali Akbar Miran Beigi, Majid Abdouss, Amir Vahid

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Hydrogen sulfide is the most toxic gas of crude oil. Adsorption is an energy-efficient process used to remove undesirable compounds such as H2S in gas or liquid streams by passing the stream through a media bed composed of an adsorbent. In this study, H2S of Iran crude oil was separated via cold stripping then zinc incorporated MCM-41 was synthesized via an in-situ method. ZnO functionalized mesoporous silica samples were characterized by XRD, N2 adsorption and TEM. The obtained results of adsorption of H2S showed superior ability of all the materials and with an increase in ZnO amount adsorption was increased.

Keywords: MCM-41, ZnO, H2S removal, adsorption

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Authors: Seungmin Shin, Jin-Baek Kim

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Hematite (α-Fe2O3) has very good semiconducting properties with a band gap of 2.1 eV and is antiferromagnetic. Due to its electrochemical stability, low toxicity, wide abundance, and low-cost, hematite, it is a particularly attractive material for photoelectrochemical cells. Additionally, hematite has also found applications in gas sensing, field emission, heterogeneous catalysis, and lithium-ion battery electrodes. Here, we discovered a new universal top-down method for the synthesis of one-dimensional hematite nanowire arrays. Various shapes and lengths of hematite nanowire have been easily fabricated over large areas by sequential processes. The obtained hematite nanowire arrays are promising candidates as photoanodes in photoelectrochemical solar cells.

Keywords: hematite, lithography, nanowire, top-down process

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