Bulk Scale Production Research Articles

Activating Methanol for Chemoselective Transfer Hydrogenation of Chalcones Using an SNS-Ruthenium Complex

AbstractMethanol is gaining popularity as a transfer-hydrogenating agent in catalytic reduction reactions because of its bulk-scale production and inexpensive nature. Current research interests include the utilization of methanol as a safe and sustainable hydrogen source for chemical synthesis and drug development. In particular, the chemoselective reduction of α,β-unsaturated ketones is of great interest because of their prevalence in many natural products. We investigated the potential application of acridine-derived SNS-Ru pincer complexes in methanol activation for chemoselective reduction of chalcones. Our developed catalytic system showed broad substrate tolerance, including substrates containing reducible functional groups. Control experiments and postsynthetic applications are also highlighted.

Nucleotide-based regenerated fiber production using salmon (Oncorhynchus keta) milt waste by solution spinning

The use of nucleic acid-derived fibers has not been developed in contrast to the traditional use of polysaccharide- and protein-based fibers in daily life. Salmon, Oncorhynchus keta, is an abundant fishery resource, and its milt contains a huge amount of DNA. Most of the milt is discarded because it degrades easily and is unsuitable for food consumption. DNA-based fibers are expected to possess functionality and mechanical strength because DNA is a polyanion with a high molecular weight. Here, using DNA extracted from the salmon milt, we produced nucleotide-based fibers. A solution spinning system was applied using ethanol as a coagulant. Adding the salt to the dope solution reduced the solubility of DNA, which was essential for the successful spinning of DNA-based fibers. The obtained fibers became insoluble in water by ultraviolet (UV) exposure. Fibril-like structures were detected on the fracture surface, and humidity influenced the conformational structure. This study focuses on the bulk-scale production of biodegradable DNA-based fibers. Therefore, it can be used not only for clothing and filters but also as a functional material to remove harmful pollutants released into the ocean, such as heavy metal ions and aromatic derivatives.

Strategies for Making High-Performance Artificial Spider Silk Fibers.

Artificial spider silk is an attractive material for many technical applications since it is a biobased fiber that can be produced under ambient conditions but still outcompetes synthetic fibers (e.g., Kevlar) in terms of toughness. Industrial use of this material requires bulk-scale production of recombinant spider silk proteins in heterologous host and replication of the pristine fiber's mechanical properties. High molecular weight spider silk proteins can be spun into fibers with impressive mechanical properties, but the production levels are too low to allow commercialization of the material. Small spider silk proteins, on the other hand, can be produced at yields that are compatible with industrial use, but the mechanical properties of such fibers need to be improved. Here, the literature on wet-spinning of artificial spider silk fibers is summarized and analyzed with a focus on mechanical performance. Furthermore, several strategies for how to improve the properties of such fibers, including optimized protein composition, smarter spinning setups, innovative protein engineering, chemical and physical crosslinking as well as the incorporation of nanomaterials in composite fibers, are outlined and discussed.

Eco-Friendly Synthesis of Wrinkle-Free Ultra-Flat Multi-Layer Graphene by Femtosecond Laser Irradiation of Graphite Under Ambient Conditions

Here, we report a single-step, high-yield technique for producing planar sheets of wrinkle-free multi-layer graphene (MLG) under ambient conditions by ablation of graphite powder dispersed in ethanol using a femtosecond laser. The parameters for the synthesis of MLG have been optimized and established. The number of layers and quality of MLG produced at several laser fluences (39.4 J/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , 98.72 J/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , 197.45 J/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , 296.16 J/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ) was established based on detailed characterization using field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HRTEM) with selected area electron diffraction (SAED), atomic force microscopy (AFM), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FTIR). Wrinkle-free, ultra-flat crystalline MLG sheets with 2-12 layers were produced in each case with an average lateral dimension of ∼1-3 μm. The associated oxy- functional groups were characterized and quantified using FTIR and XPS. The highest percentage of sp <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> C atoms and C/O ratio for MLG was achievedat the lowest laser fluence. The higher the laser fluence higher the defects produced in the MLG sheets. The technique produces zero chemical waste, has a very high yield of ∼ 95%, and is promising for bulk-scale production of MLG.

Engineered Spider Silk Proteins for Biomimetic Spinning of Fibers with Toughness Equal to Dragline Silks.

Spider silk is the toughest fiber found in nature, and bulk production of artificial spider silk that matches its mechanical properties remains elusive. Development of miniature spider silk proteins (mini-spidroins) has made large-scale fiber production economically feasible, but the fibers' mechanical properties are inferior to native silk. The spider silk fiber's tensile strength is conferred by poly-alanine stretches that are zipped together by tight side chain packing in β-sheet crystals. Spidroins are secreted so they must be void of long stretches of hydrophobic residues, since such segments get inserted into the endoplasmic reticulum membrane. At the same time, hydrophobic residues have high β-strand propensity and can mediate tight inter-β-sheet interactions, features that are attractive for generation of strong artificial silks. Protein production in prokaryotes can circumvent biological laws that spiders, being eukaryotic organisms, must obey, and the authors thus design mini-spidroins that are predicted to more avidly form stronger β-sheets than the wildtype protein. Biomimetic spinning of the engineered mini-spidroins indeed results in fibers with increased tensile strength and two fiber types display toughness equal to native dragline silks. Bioreactor expression and purification result in a protein yield of ≈9gL-1 which is in line with requirements for economically feasible bulk scale production.

A nanosheet-based combination emulsifier system for bulk-scale production of emulsions with elongated droplets and long-term stability

In this study, we investigate the emulsion type, droplet morphology and emulsion stability that can be achieved using a novel combination emulsifier system which consists of water-soluble α-zirconium phosphate tetrabutyl ammonium (α-ZrP-TBA) nanosheets as the particulate emulsifier and Span 80 as the oil-soluble emulsifier, with the two emulsifiers present in distinct phases. We find that water-in-oil emulsions were formed for water volume fractions < 0.3, and oil-in-water (O/W) emulsions were formed for water volume fractions > 0.3. This phase inversion point was found to be the same irrespective of whether the emulsifier was only Span 80 or only nanosheet or their combination. Varying the concentrations of either surfactant or the nanosheet did not alter the phase inversion point. The emulsions with the greatest stability against creaming were formed using the combination emulsifier and were found to be the O/W type, that were stable for 3 months. Interestingly, we find that droplets in these stable emulsions were nonspherical, with the aspect ratio of droplets increasing with nanosheet and Span 80 concentration, suggesting a synergistic interaction between the two emulsifiers to create elongated droplets. We perform capillary neck thinning experiments to show that the combination emulsifier system offers unique interfacial properties that are different from either emulsifier alone, suggesting that interfacial jamming could occur to produce elongated droplets. Taken together, our results suggest a novel route to bulk-scale production of O/W emulsions that have long-term emulsion stability with unique droplet morphology.

Nanocatalyst-Fe3O4@SiO2 mediated efficient isoxazole cyclization and bulk synthesis

Isoxazoles are found to be key components in the area of medicinal chemistry and agriculture. Reaction yields of cyclized derivatives is low (∼30%) and when reaction temperature goes beyond ambient temperature, decomposition reactions lead to further reduction in yield. Herein, we report silica functionalized magnetic nanomaterials as an inert catalyst for isoxazole cyclization. The model system chosen is 1, 2-benzisoxazole. The key role of Fe3O4@SiO2 particles was to provide inert surface as well as lower the cyclization temperature. The present protocol does not include any column purification and 1,2-benzisoxazole are obtained in good yield. Silica surface interacts with lone pairs present on oxygen. In this work we found that acidic surface of silica has additional role for cyclization under basic conditions. In this protocol, the reaction of hydroxylamine-o-sulphonic acid with salicylaldehyde results in the formation of N-O bond followed by ring cyclization with the assistance of acidic surface of Fe3O4@SiO2. The 40 nm sized Fe3O4@SiO2 favoured the maximum yield attributed to the density of active sites. Conceivably reported work results significant improvement in yield (60 %), which is substantial in bulk scale production of drugs.

An Efficient Synthesis of 4-Aminomethyl-1-(2-Phenylethyl)-Piperidin-4-ol: A Key Intermediate in Fenspiride HCl Synthesis

The article confers a scalable manufacturing process of Fenspiride HCl. 4-aminomethyl-1-(2-phenylethyl)-piperidin-4-ol is the main building block in Fenspiride HCl synthesis. The reported reagents for 4-aminomethyl-1-(2-phenylethyl)-piperidin-4-ol synthesis are costly, explosive, highly toxic, produce hazardous waste, and also need to be handled with most care. The paper introduces aqueous ammonia as an alternate reagent in Fenspiride HCl and used in 4-aminomethyl-1-(2-phenylethyl)-piperidin-4-ol synthesis. The new green chemistry aspect makes the process environment-friendly and cheaper. It also eliminates toxic, sensitive, and hazardous reagents and makes the process safe on uncomplicated on bulk scale production.&#x0D; The high pure Fenspiride HCl is obtained by following this process and meets the ICH limits with good yield.

The Future of Flash Graphene for the Sustainable Management of Solid Waste.

Graphene research has steadily increased, and its commercialization in many applications is becoming a reality because of its superior physicochemical properties and advances in synthesis techniques. However, bulk-scale production of graphene still requires large amounts of solvents, electrochemical treatment, or sonication. Recently, a method was discovered to convert bulk quantities of carbonaceous materials to graphene using flash Joule heating (FJH) and, so named, flash graphene (FG). This method can be used to turn various solid wastes containing the prerequisite element carbon into FG. Globally, more than 2 billion tons of municipal solid waste (MSW) are generated every year and, in many municipalities, are becoming unmanageable. The most commonly used waste management methods include recycling, composting, anaerobic digestion, incineration, gasification, pyrolysis, and landfill disposal. However, around 70% of global waste ends up in landfills or open dumps, while the rest is recycled, composted, or incinerated. Even the various waste valorization techniques, such as pyrolysis and gasification, produce some waste residues that have their ultimate destination in landfills. Thus, technologies that can minimize waste volume or convert waste into valuable products are required. The thermal treatment process of FJH for FG production provides both waste volume reduction and valorization in the form of FG. In this Perspective, we provide an overview of FJH and its possible applications in various types of waste conversion/valorization. We describe the typical current MSW management system as well as the potential for creating FG at various stages and propose a schematic plan for the incorporation of FG in MSW management. We also analyze the strengths, weaknesses, opportunities, and threats of MSW as an FG precursor in terms of technical, economic, environmental, and social sustainability. This valuable waste valorization and management strategy can help achieve near-zero waste and an economy-boosting MSW management system.

Mixed-Matrix Membrane Fabrication for Water Treatment.

In recent years, technology for the fabrication of mixed-matrix membranes has received significant research interest due to the widespread use of mixed-matrix membranes (MMMs) for various separation processes, as well as biomedical applications. MMMs possess a wide range of properties, including selectivity, good permeability of desired liquid or gas, antifouling behavior, and desired mechanical strength, which makes them preferable for research nowadays. However, these properties of MMMs are due to their tailored and designed structure, which is possible due to a fabrication process with controlled fabrication parameters and a choice of appropriate materials, such as a polymer matrix with dispersed nanoparticulates based on a typical application. Therefore, several conventional fabrication methods such as a phase-inversion process, interfacial polymerization, co-casting, coating, electrospinning, etc., have been implemented for MMM preparation, and there is a drive for continuous modification of advanced, easy, and economic MMM fabrication technology for industrial-, small-, and bulk-scale production. This review focuses on different MMM fabrication processes and the importance of various parameter controls and membrane efficiency, as well as tackling membrane fouling with the use of nanomaterials in MMMs. Finally, future challenges and outlooks are highlighted.

Statistical Optimization and Bulk Scale Validation of the Effects of Cationic Pre-treatment of Cotton Fabric for Digital Printing with Reactive Dyes

ABSTRACT Digital printing has the potential of enabling cleaner printing or even dyeing of cotton fabrics. However, whilst effluent-free digital printing and dyeing of synthetic textile fabrics have seen some success, the same remain elusive for cotton fabrics. The study reported in this paper aimed to optimize the process parameters of cationic pre-treatment with a view to creating a cleaner cotton fabric digital printing process that could be sustainably implemented at bulk-scale production. Thus, process variables were screened using the one-factor-at-a-time approach to select optimum experimental regions. A Box–Behnken design was used to investigate the combined effect of selected factors namely amount of thickener (150–200 g/L), urea (75–125 g/L) and alkali (10–20 g/L) on the color strength, dye fixation and ink penetration of cationized and digital-printed cotton fabrics. The significant models showed excellent fitting of the data. The optimum levels of the factors, namely, amount of thickener, urea and alkali were found 200 g/L, 125 g/L and 10 g/L, respectively. The bulk-scale experiments carried out at optimum levels have shown that an average of ca. 52% of reactive ink, 37.5% of urea and 50% of alkali can be saved by digital printing of cationized cotton along with generation of nearly colorless effluent.

Natural surfactants assisted an efficient synthesis of tetrahydro-β-carbolines

An expeditious protocol for the synthesis of structurally diversified β-carboline derivatives has been reported using a readily available natural surfactant medium. The synthesis of β-carboline derivatives in good yields under optimized conditions was carried out by the reaction of tryptamine with aldehydes in an aqueous extract of Acacia Concinna pods. The use of an aqueous medium, ease of purification, good yield and cost-effective reaction suggest for bulk scale production β-carboline derivatives.

Regulation of the Peroxidase-Like Activity of nGO, MoS2 and WS2 Nanozymes by Using Metal Cations.

Two dimensional nanoparticles (2D-NPs) along with other nanoscale materials have been deemed to be the next generation of artificial enzymes (nanozymes). The low-cost bulk-scale production, ease of storage and modification of such nanomaterials have given nanozymes an advantage over traditional enzymes. Many studies have been aimed at developing methods to increase the performance of these nanozymes, and also identify interfering agents. To investigate the interference of a number of metal cations, we studied the effect of Ti2+ , Fe2+ , Ag+ , Hg2+ , Co2+ , Cu2+ , Ni2+ , Pb2+ , Ca2+ , Zn2+ and Mn2+ in a nanozyme assays of 2D-NPs using ABTS radical formation. Ti2+ , Co2+ , Cu2+ , Ni2+ , Ca2+ , Zn2+ and Mn2+ ions did not display any notable effect on the peroxidase-like activity of nGO, MoS2 and WS2 2D-NPs. However, Fe2+ , Ag+ , Hg2+ and Pb2+ ions' effects on the overall ABTS reaction were significant enough to be visualised by partial least square discriminant analysis (PLSDA). We report that, similar to that of many natural enzymes, the nanozyme activity of 2D-NPs is regulated by a number of metal cations allowing their identification and discrimination by using a statistical analysis tool.

Sustainable dyeing of nylon fabric with acid dyes in decamethylcyclopentasiloxane (D5) solvent for improving dye uptake and reducing raw material consumption

In this investigation, a solvent dyeing approach was studied to minimize the consumption of water and dyes and to reduce waste effluent by the use of Decamethylcyclopentasiloxane (D5) solvent. To analyze D5 solvent ability to penetrate nylon fiber, XPS analysis was carried out. The feasibility of the use of D5 solvent as dyeing media was also assessed by measuring the effect of D5 processing on fabric chemical, thermal, and crystalline properties by FTIR, TGA, DSC, and XRD analysis. The effect of D5 solvent processing on the mechanical properties of nylon was analyzed by measuring the change in fabric strength and elongation. The basic dyeing procedure for nylon with acid dyes has been developed. It was found that D5 can penetrate the nylon fiber interior and both aqueous as D5 solvent have a similar effect on fabric properties. When nylon fabric was dyed in D5 solvent with acid dyes, 100% dye exhaustion was achieved for all three dyes. By replacing water with D5 solvent as dyeing media for AR249, AB83, and AO67 dyes, the color strength reached 11.44, 25.24, and 19.07 from 7.47, 19.18 and 15.48, respectively. Furthermore, the same D5 bath, without recycling or purification was used successfully in 5 repeated dyeing cycles as no process auxiliaries were added in dyebath. Therefore, this compatibility of D5 with existing acid dye range and dyeing machinery makes it readily applicable for bulk scale production.

Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects

177Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177Lu-DOTA-TATE using medium specific activity 177Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility. In an optimized protocol, 177Lu-DOTA-TATE synthesis was carried out by direct heating of 177LuCl3 (Sp. act. 740-1110 GBq/mg) with DOTA-TATE peptide (1.5-3.0 equivalents) in ammonium acetate buffer (0.2 M) containing 2,5-dihydroxy benzoic acid (gentisic acid). Thereafter, the crude labeled product was purified using a Sep-Pak® C18 column and diluted with acetate buffer-gentisic acid (1.5% w/v) solution to final radioactive concentration of 740 MBq/mL. This was further sterilized and dispensed as 7.4 GBq patient dose/vial with 2 days postformulation calibration. A peptide/metal ratio of 1.5-3.0 is essential for complexation wherein radiolabeling yields >90% are obtained minimizing free 177Lu waste. For formulation of 7.4 GBq patient dose (2 days postproduction), even specific activity of about 555 GBq/mg was found to be adequate for the radiometal. The ready-to-use 740 MBq/mL 177Lu-DOTA-TATE formulation with gentisic acid (1.5% w/v) is observed to be safe for human use for more than 1 week (radiochemical purity >98%) from the day of production when stored at -70°C. However, the target specificity may get affected beyond 2 days as the total peptide content for 7.4 GBq dose may exceed the critical peptide limit of 300 μg. Patient treatment carried with several batches of present formulation in diseased NET patients exhibited desired distribution at the tumor and its metastatic site. A ready-to-use formulation of 177Lu-DOTA-TATE was successfully prepared and optimized for regular bulk scale production and supply to distant nuclear medicine centers.

Tuning the surface charge of 2D oxide nanosheets and the bulk-scale production of superlatticelike composites.

The surface charge of various anionic unilamellar nanosheets, such as graphene oxide (GO), Ti0.87O2(0.52-), and Ca2Nb3O10(-) nanosheets, has been successfully modified to be positive by interaction with polycations while maintaining a monodispersed state. A dilute anionic nanosheet suspension was slowly added dropwise into an aqueous solution of high molecular weight polycations, which attach on the surface of the anionic nanosheets via electrostatic interaction. Surface modification and transformation to positively charged nanosheets were confirmed by various characterizations including atomic force microscopy and zeta potential measurements. Because the sizes of the polycations used are much larger than the nanosheets, the polymer chains may run off the nanosheet edges and fold to the fronts of the nanosheets, which could be a reason for the continued dispersion of the modified nanosheets in the suspension. By slowly adding a suspension of polycation-modified nanosheets and pristine anionic nanosheet dropwise into water under suitable conditions, a superlatticelike heteroassembly can be readily produced. Characterizations including transmission electron microscopy and X-ray diffraction measurements provide evidence for the formation of the alternately stacked structures. This approach enables the combination of various pairs of anionic nanosheets with different functionalities, providing a new opportunity for the creation of unique bulk-scale functional materials and their applications.

Material Processing of Chemically Modified Graphene: Some Challenges and Solutions

Graphene-based sheets show promise for a variety of potential applications, and researchers in many scientific disciplines are interested in these materials. Although researchers have developed many ways of generating single atomic layer carbon sheets, chemical exfoliation of graphite powders to graphene oxide (GO) sheets followed by deoxygenation to form chemically modified graphene (CMG) offers a promising route for bulk scale production. The materials processing, which we broadly define as the physical and chemical means to tailor a material's chemical and microstructures, enables us to control the properties in bulk CMG materials. For example, by processing CMG sheets in different solvents, we can make thin films, blend CMG sheets with other materials, and modify them by chemical reactions. Materials processing methods also allow us to control the interactions between CMG sheets for the assembly of large scale two- or three-dimensional structures with desirable microstructures. This Account highlights a few problems associated with large scale production and processing of GO and CMG. First, we briefly discuss the potential fire risk of GO and CMG when alkaline salt byproducts are not completely removed. These impurities can catalyze carbon combustion. We introduce an improved purification procedure that effectively removes the byproducts and speeds up the production. Next, we address the challenges of imaging GO and CMG sheets on common substrates such as glass and plastics using standard microscopy methods. We have introduced a new technique fluorescence quenching microscopy (FQM), which allows us to observe graphene-based sheets with both high throughput and high contrast on arbitrary substrates and even in solution. Then we focus on how to prevent aggregation in CMG. Aggregation greatly reduces the material processability and accessible surface area, which degrades the material properties. We introduce two strategies to reduce aggregation by (i) reducing the lateral dimension of the sheets to nanometer range to enhance their colloidal stability and (ii) crumpling the sheets into paper ball-like, fractal-dimensional particles to make them aggregation-resistant in both solvents and solid state, even after mechanical compression. Solutions to these material processing challenges can pave the way for further research and development. We hope that the tools and strategies presented in this Account can facilitate the processing and property control of this promising material.

Bulk scale production of carbon nanofibers in an economical way

An economical route for the scalable production of carbon nanofibers (CNFs) on a sodium chloride support has been developed. CNFs have been synthesized by chemical vapor deposition (CVD) method by using metal formate as catalyst precursors at 680°C. Products were characterized by SEM, TEM, Raman spectroscopy and XRD method. By thermal analysis, the purity of the as grown products and purified products were determined. This method avoids calcination and reduction process which was employed in commercial catalysts such as metal oxide or nitrate. The problems such as detrimental effect, environmental and even cost have been overcome by using sodium chloride as support. The yield of CNFs up to 7800 wt.% relative to the nickel catalyst has been achieved in the growth time of 15 min. The advantage of this synthesis technique is the simplicity and use of easily available low cost precursors.

Reducing Graphene Oxide via Hydroxylamine: A Simple and Efficient Route to Graphene

Bulk-scale production of individual graphene sheets is still challenging although several methodologies have been developed. We report here a rapid and cost-effective approach to reduction of graphene oxide (GO) using hydroxylamine as a reductant. We demonstrated that the reduction of GO with hydroxylamine could take place quickly under a mild condition, and the as-produced graphene sheet showed high electrical conductivity, fair crystalline state, and admirable aqueous dispersibility without using any stabilizing reagents. A mechanism for removal of epoxide and hydroxyl groups from GO by hydroxylamine has been proposed. Comparing with other reported methods, the reduction of GO with hydroxylamine should be a preferable route to bulk-scale production of the graphene because it is simple, efficient, and cost-effective.

Arrested coalescence in Pickering emulsions

When two emulsion drops begin to coalesce, their complete fusion into a single spherical drop can sometimes be arrested in an intermediate shape if a rheological resistance offsets the Laplace pressure driving force. Arrested coalescence of droplets is important, both for its broad impact on commercial food production as well as its potential for fabricating novel anisotropic colloidal microstructures. We use a micromanipulation technique to demonstrate the dynamics of arrested coalescence between droplets with interfacially adsorbed colloids. Surface coverage of the droplets is precisely determined by a capillary aspiration technique and then their coalescence is studied in situ. Depending on their surface coverage, droplets can experience total coalescence, arrested coalescence or total stability. We use microscopic observations along with geometrical packing arguments to confirm that coalescence is arrested due to close-packed jamming of particles. The anisotropic Laplace stress within the arrested structure is balanced by the elastic modulus of the jammed interface and thus further relaxation of the arrested structure is halted. Precise mapping of the arrested coalescence regime at a microscopic scale helps us to anticipate its effects on bulk scale production of such anisotropic colloidal structures.