\\n\\n
Dr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\\n\\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\\n\\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\\n\\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\\n\\nThank you all for being part of the journey. 5,000 times thank you!
\\n\\nNow with 5,000 titles available Open Access, which one will you read next?
\\n\\nRead, share and download for free: https://www.intechopen.com/books
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Preparation of Space Experiments edited by international leading expert Dr. Vladimir Pletser, Director of Space Training Operations at Blue Abyss is the 5,000th Open Access book published by IntechOpen and our milestone publication!
\n\n"This book presents some of the current trends in space microgravity research. The eleven chapters introduce various facets of space research in physical sciences, human physiology and technology developed using the microgravity environment not only to improve our fundamental understanding in these domains but also to adapt this new knowledge for application on earth." says the editor. Listen what else Dr. Pletser has to say...
\n\n\n\nDr. Pletser’s experience includes 30 years of working with the European Space Agency as a Senior Physicist/Engineer and coordinating their parabolic flight campaigns, and he is the Guinness World Record holder for the most number of aircraft flown (12) in parabolas, personally logging more than 7,300 parabolas.
\n\nSeeing the 5,000th book published makes us at the same time proud, happy, humble, and grateful. This is a great opportunity to stop and celebrate what we have done so far, but is also an opportunity to engage even more, grow, and succeed. It wouldn't be possible to get here without the synergy of team members’ hard work and authors and editors who devote time and their expertise into Open Access book publishing with us.
\n\nOver these years, we have gone from pioneering the scientific Open Access book publishing field to being the world’s largest Open Access book publisher. Nonetheless, our vision has remained the same: to meet the challenges of making relevant knowledge available to the worldwide community under the Open Access model.
\n\nWe are excited about the present, and we look forward to sharing many more successes in the future.
\n\nThank you all for being part of the journey. 5,000 times thank you!
\n\nNow with 5,000 titles available Open Access, which one will you read next?
\n\nRead, share and download for free: https://www.intechopen.com/books
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6469",leadTitle:null,fullTitle:"Application of Exergy",title:"Application of Exergy",subtitle:null,reviewType:"peer-reviewed",abstract:'The main scope of this study is to emphasize exergy efficiency in all fields of industry. The chapters collected in the book are contributed by invited researchers with a long-standing experience in different research areas. I hope that the material presented here is understandable to a wide audience, not only energy engineers but also scientists from various disciplines. The book contains seven chapters in three sections: (1) "General Information about Exergy," (2) "Exergy Applications," and (3) "Thermoeconomic Analysis." This book provides detailed and up-to-date evaluations in different areas written by academics with experience in their fields. It is anticipated that this book will make a scientific contribution to exergy workers, researchers, academics, PhD students, and other scientists in both the present and the future.',isbn:"978-1-78923-267-7",printIsbn:"978-1-78923-266-0",pdfIsbn:"978-1-83881-481-6",doi:"10.5772/intechopen.70915",price:119,priceEur:129,priceUsd:155,slug:"application-of-exergy",numberOfPages:158,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"0836749bb350a373d5e2628c73539698",bookSignature:"Tolga Taner",publishedDate:"June 6th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6469.jpg",numberOfDownloads:9091,numberOfWosCitations:15,numberOfCrossrefCitations:12,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:18,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:45,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 14th 2017",dateEndSecondStepPublish:"October 5th 2017",dateEndThirdStepPublish:"December 4th 2017",dateEndFourthStepPublish:"February 22nd 2018",dateEndFifthStepPublish:"April 23rd 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner",profilePictureURL:"https://mts.intechopen.com/storage/users/197240/images/system/197240.jpg",biography:"Dr. Tolga Taner is the head of the Department of Motor Vehicles and Transportation Technology at Aksaray University, Turkey. He received a BS in Mechanical Engineering in 1998; an MS in Mechanical Engineering from Pamukkale University, Denizli, Turkey, in 2002; and a Ph.D. in Mechanical Engineering from the Gazi University of Engineering Faculty, Ankara, Turkey, in 2013. In 2018, he received the title of Associate Professor from the Inter-University Council (UAK). He also worked as a part-time lecturer in the Department of Technical Programs, Middle East Technical University, Turkey, from 2003 to 2006. His current research interests include exergy, renewable energy, and PEM fuel cells. He has published many scientific and conference papers and books. In addition, Dr. Taner has been a manager and researcher for many research projects.",institutionString:"Aksaray University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Aksaray University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"773",title:"Thermal Engineering",slug:"engineering-energy-engineering-thermal-engineering"}],chapters:[{id:"58347",title:"Introductory Chapter: Application of Exergy for All Energy Field and New Technologies",doi:"10.5772/intechopen.72683",slug:"introductory-chapter-application-of-exergy-for-all-energy-field-and-new-technologies",totalDownloads:1184,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Tolga Taner",downloadPdfUrl:"/chapter/pdf-download/58347",previewPdfUrl:"/chapter/pdf-preview/58347",authors:[{id:"197240",title:"Associate Prof.",name:"Tolga",surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],corrections:null},{id:"60258",title:"Application of Exergy: A Low-Exergy Solution to Building Heating and Cooling",doi:"10.5772/intechopen.74861",slug:"application-of-exergy-a-low-exergy-solution-to-building-heating-and-cooling",totalDownloads:1035,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Considering heat a form of energy, the mechanical theory of heat (MTH), in making this historic advance of heat’s ontological-category, made a relational-category error. The resulting energetic viewpoint of MTH sees all changes in nature as energy conversions and the problem of building heating and cooling as, quantitatively, energy-demand-and-supply problem. The IEA-ECBCS-programme introduced a correction to this energetic bias with the principle of “matching the quality levels between the energy supply and demand,” which is known as LowEx approach. A recently formulated theory of heat, the predicative entropic theory of heat (PETH), is based on the cornerstone of correct categories of heat ontologically as well as predicatively (relationally). In the new theory, heat extraction plays a central role and, therefore, changes in nature are seen in terms of spontaneous entropy growth and heat extraction as powered by entropy growth potentials (EGPs). An alternative to the IEA-ECBCS’s LowEx approach is suggested here based on heat extraction. Instead of matching of quality levels, LowEx can also be achieved by the management of natural EGPs: the combined solar and heat pump systems (S+HPs) can be transformed into LowEx S+HPs, a pure heat extraction system, by “eliminating” the energy conversion process of auxiliary heating.",signatures:"Lin-Shu Wang",downloadPdfUrl:"/chapter/pdf-download/60258",previewPdfUrl:"/chapter/pdf-preview/60258",authors:[{id:"223830",title:"Prof.",name:"Lin-Shu",surname:"Wang",slug:"lin-shu-wang",fullName:"Lin-Shu Wang"}],corrections:null},{id:"61325",title:"Exergetic Assessment in Dairy Industry",doi:"10.5772/intechopen.75028",slug:"exergetic-assessment-in-dairy-industry",totalDownloads:1221,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Food industry is one of the most energy-consuming industries. Exergy analysis for several food production lines had been the subject of some studies in the past. However, dairy industry has a significant importance among food industry from energetic point of view since it covers many heating and cooling processes. Energy and exergy analyses are commonly used techniques for performance assessment of thermal system where exergy analysis is known as the powerful tool. In this context, exergy calculation methodology and a review of exergetic assessment in dairy industry are the subject of this study for the first time to the best of author’s knowledge. In this chapter, first of all, exergy analysis methodology is presented, and next, assessment of exergy analysis of some dairy processes including milk pasteurization, milk powder process, flavored yoghurt production, yoghurt production and yoghurt drink processes are reviewed, comprehensively. Application of the exergy analysis in dairy industry supplies possibility to perform exergetic design, simulation, analysis and performance assessment.",signatures:"Seda Genc",downloadPdfUrl:"/chapter/pdf-download/61325",previewPdfUrl:"/chapter/pdf-preview/61325",authors:[{id:"221734",title:"Dr.",name:"Seda",surname:"Genç",slug:"seda-genc",fullName:"Seda Genç"}],corrections:null},{id:"59710",title:"Advanced Exergy Analysis of an Integrated SOFC-Adsorption Refrigeration Power System",doi:"10.5772/intechopen.74201",slug:"advanced-exergy-analysis-of-an-integrated-sofc-adsorption-refrigeration-power-system",totalDownloads:1045,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In this chapter, an exergy analysis applied to a solid oxide fuel cell (SOFC)/vapor adsorption refrigeration (VAR) system is presented. The influences of four significant parameters (current density, inlet fuel temperature, fuel utilization and steam-to-carbon ratio) on the exergy efficiency of both the SOFC stack and the SOFC-VAR system are investigated. In order to do so, a mathematical model is constructed in Engineering Equation Solver (EES) software to generate the simulations. The analysis shows that the calculated exergy efficiency is around 8% lower than the energy efficiency for both cases. Moreover, it is found that most of the causes of irreversibilities in the system are due to electronic and ionic conduction in the components. It is also shown that the exergy efficiency is substantially sensitive to fuel inlet temperature, which is evidenced by a bending-over behavior. Finally, in accordance with the calculated efficiency defects, the main exergy destructions are present in the heat exchangers, the SOFC, the afterburner and the generator.",signatures:"Victor Hugo Rangel-Hernández, Andrés M. Niño-Avendaño, José J.\nRamírez-Minguela, Juan M. Belman-Flores and Francisco Elizalde-\nBlancas",downloadPdfUrl:"/chapter/pdf-download/59710",previewPdfUrl:"/chapter/pdf-preview/59710",authors:[{id:"145219",title:"Dr.",name:"Victor Hugo",surname:"Rangel-Hernandez",slug:"victor-hugo-rangel-hernandez",fullName:"Victor Hugo Rangel-Hernandez"},{id:"145857",title:"Dr.",name:"Francisco",surname:"Elizalde-Blancas",slug:"francisco-elizalde-blancas",fullName:"Francisco Elizalde-Blancas"},{id:"202266",title:"Dr.",name:"Juan Manuel",surname:"Belman-Flores",slug:"juan-manuel-belman-flores",fullName:"Juan Manuel Belman-Flores"},{id:"227040",title:"Dr.",name:"Andrés Mauricio",surname:"Niño-Avendaño",slug:"andres-mauricio-nino-avendano",fullName:"Andrés Mauricio Niño-Avendaño"},{id:"227401",title:"Dr.",name:"José De Jesús",surname:"Ramírez-Minguela",slug:"jose-de-jesus-ramirez-minguela",fullName:"José De Jesús Ramírez-Minguela"}],corrections:null},{id:"59000",title:"New Exergetic Methodology to Promote Improvements in nZEB",doi:"10.5772/intechopen.73153",slug:"new-exergetic-methodology-to-promote-improvements-in-nzeb",totalDownloads:997,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The benefits obtained through the application of exergy concept in buildings are currently known, since they contribute to the proper use of energy as well as to a better adequacy of the different energy qualities taking part in a facility. Besides, an exergy analysis supports the identification of both the economic and environmental cost formation in every phase of the energy transformation chain. Those type of studies are known as exergoeconomic and exergoenvironmental analyses. In this work, a nearly zero energy buildings (nZEB) single-family dwelling is analyzed, where heating and DHW exergy demands are hourly calculated. A full exergetic analysis of its building envelope and thermal facility is carried out and exergoeconomic and exergoenvironmental analyses are applied. The aim of this study is to show the enormous possibilities for the energy efficiency improvement that still exist, which cannot be appreciated through a common energetic analysis (being the facility’s energetic efficiency of 81% and exergetic one of 13%). In addition, the results of this study indicate the location and the correct assessment of the real inefficiencies.",signatures:"Ana Picallo-Perez, Juan-Maria Hidalgo-Betanzos and Jose-Maria\nSala-Lizarraga",downloadPdfUrl:"/chapter/pdf-download/59000",previewPdfUrl:"/chapter/pdf-preview/59000",authors:[{id:"223909",title:"Mrs.",name:"Ana",surname:"Picallo-Perez",slug:"ana-picallo-perez",fullName:"Ana Picallo-Perez"}],corrections:null},{id:"60220",title:"Application of Exergy Analysis to Energy Systems",doi:"10.5772/intechopen.74433",slug:"application-of-exergy-analysis-to-energy-systems",totalDownloads:2416,totalCrossrefCites:9,totalDimensionsCites:13,hasAltmetrics:0,abstract:"Exergy analysis is a practical approach to evaluate the merit of energy conversion or distribution processes and systems. With the aid of an energy analysis, the performance of an energy conversion system cannot be evaluated efficiently and precisely. But, an exergy analysis complements and enhances an energy analysis. Exergy analysis involves the application of exergy concepts, balances, and efficiencies to evaluate and improve energy and other systems. Many scientists suggest that processes or sytems can be well evaluated and improved using exergy analysis in addition to or in place of energy analysis. Application of exergy analysis has given us more beneficial opportunities through a big part of a wide range of processes and systems particularly for the evaluation of energy systems and technologies as well as an environmental impact in all existing thermal and nuclear power plants. Conventional energy technologies, especially for power generation plants, have made numerous energy and exergy analyses and have produced beneficial results. Also, the use of energy and exergy analyses for advanced nuclear energy technologies can be expected to provide meaningful insights into performance that can assist in achieving optimal design concepts. Finally, explaining the analysis of thermal and nuclear power plant systems deals with exergetic approach.",signatures:"Rauf Terzi",downloadPdfUrl:"/chapter/pdf-download/60220",previewPdfUrl:"/chapter/pdf-preview/60220",authors:[{id:"222042",title:"Dr.",name:"Rauf",surname:"Terzi",slug:"rauf-terzi",fullName:"Rauf Terzi"}],corrections:null},{id:"59041",title:"Exergetic Costs for Thermal Systems",doi:"10.5772/intechopen.73089",slug:"exergetic-costs-for-thermal-systems",totalDownloads:1193,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Exergy costing to estimate the unit cost of products from various power plants and refrigeration system is discussed based on modified-productive structure analysis (MOPSA) method. MOPSA method provides explicit equations from which quick estimation of the unit cost of products produced in various power plants is possible. The unit cost of electricity generated by the gas-turbine power plant is proportional to the fuel cost and inversely proportional to the exergetic efficiency of the plant and is affected by the ratio of the monetary flow rate of non-fuel items to the monetary flow rate of fuel. On the other hand, the unit cost of electricity from the organic Rankine cycle power plant with heat source as fuel is proportional to the unit cost of heat and the ratio of the monetary flow rate of non-fuel items to the generated electric power, independently. For refrigeration system, the unit cost of heat is proportional to the consumed electricity and inversely proportional to the coefficient of performance of the system, and is affected by the ratio of the monetary flow rate of non-fuel items to the monetary flow rate of consumed electricity.",signatures:"Ho-Young Kwak and Cuneyt Uysal",downloadPdfUrl:"/chapter/pdf-download/59041",previewPdfUrl:"/chapter/pdf-preview/59041",authors:[{id:"15336",title:"Dr.",name:"Ho-Young",surname:"Kwak",slug:"ho-young-kwak",fullName:"Ho-Young Kwak"},{id:"235337",title:"Prof.",name:"Cuneyt",surname:"Uysal",slug:"cuneyt-uysal",fullName:"Cuneyt Uysal"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6285",title:"Proton Exchange Membrane Fuel Cell",subtitle:null,isOpenForSubmission:!1,hash:"ed010c881a38d577f89ccb714c17f785",slug:"proton-exchange-membrane-fuel-cell",bookSignature:"Tolga Taner",coverURL:"https://cdn.intechopen.com/books/images_new/6285.jpg",editedByType:"Edited by",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editedByType:"Edited by",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. 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His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). 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The germinal matrix (GM) is a specialized layer of glial and neuronal precursor cells in the periventricular region of the brain with high metabolic activity, which is strongly dependent on its rich vascularity and rapid angiogenesis [1]. The dense and fragile vasculature makes GM selectively vulnerable to hemorrhage. Germinal matrix – intraventricular hemorrhage (GM-IVH) is the most common type of intracranial hemorrhage in preterm infants. A combination of increased perinatal stress, poor cerebral autoregulation, and inherent fragility of the nascent vessels in the germinal matrix increases the likelihood of the development of GM-IVH in preterm infants. Also, there is evidence of occurrence in-utero and among full-term infants, however, such cases are rare [2]. The germinal matrix disappears by 36–37 weeks of gestation (wg), so GM-IVH is more likely in preterm infants than full term.
The global incidence of GM-IVH among preterm infants ranges from 14.7% to 44.7%, with variations across gestational age groups, countries, and antenatal and neonatal care [3]. The widespread use of cranial ultrasonography since the early 1980s, increasing knowledge of risk factors, antenatal steroid usage, and improved intensive care have improved incidence, survival, and morbidity of GMH [4]. However, GMH continues to remain a significant healthcare issue in preterm infants and a recognizable cause of long-term neurological and behavioral issues in survivors.
Developmentally, GM is located in the ganglionic eminence of the brain and is most pronounced in the caudate nucleus. The thickness and density of GM vasculature are higher than other brain areas and begin to decrease after 24 weeks of gestation (wg) and almost disappear at 36–37 wg with increasing fetal maturity [1, 5]. A significant bleed in the highly vascular GM breaks the associated ependyma to involve the lateral cerebral ventricle constituting intraventricular hemorrhage (IVH) [6, 7]. The incidence of GMH-IVH increases with decreasing gestation age at birth in preterm infants [8, 9, 10].
The pathogenesis of GM-IVH is complex and heterogeneous. The blood–brain barrier (BBB) associated with GM vasculature is distinct from the remaining areas in the brain due to diminished: 1) pericytes, 2) fibronectin in the basal lamina, and 3) GFAP (glial fibrillary acidic protein) in astrocyte endfeet (Figure 1). The paucity of three essential components of the BBB leads to the altered structural integrity of GM vasculature. First, pericytes play an essential role in BBB development, especially in early angiogenesis, extracellular matrix production, and endothelial maturation [11]. The paucity of pericytes in GM is associated with diminished levels of TGF-β [12] and predisposition to hemorrhage in dilatated blood vessels in experimental models [13]. Second, fibronectin, a high molecular weight glycoprotein, is selectively deficient in the GM basement membrane [14]. Fibronectin polymerizes to provide structural integrity to blood vessels and is dependent on TGF-β for its upregulation. While other basement membrane components, including Collagen I, II, IV, laminin, and perlecan, are similar to other components in the human brain [14, 15]. Third, astrocytes provide vascular integrity by sheathing the predominance of the BBB with their GFAP rich extensions (endfeet). Autopsy studies in premature infants show decreased GFAP expressing astrocyte endfeet in GM than cerebral cortex and white matter [16]. These make the blood–brain barrier fragile and more susceptible to hemorrhage.
Diagrammatic representation of the coronal section of a preterm brain to highlight the factors contributing to the labile structure of the blood brain barrier in the germinal matrix and pathogenesis of the GM-IVH.
Microscopically the GM vasculature has been described as circular in coronal sections, compared to elongated and flat vessels in other areas of the brain, representing the immaturity of the vessels from rapid angiogenesis and high endothelial turnover [17]. In addition, immunofluorescence and electron microscopy have shown a paucity of pericytes in the GM vascular environment [12].
Finally, fluctuations in cerebral blood flow precipitate into hemorrhage in the delicate GM. In addition, defects in the hemostatic mechanisms expectantly promote hemorrhage [6, 7].
Germinal matrix cells being metabolically active precursor neuronal and glial cells in the early stages of maturation demand a specialized and rich blood supply. This requirement is met by accelerated angiogenesis dependent on high levels of vascular endothelial growth factors (VEGF) and angiopoietin-2 and low expression of TGF-β [1]. Also, the GM is in a state of relative hypoxia, a driving force for continuous angiogenesis [6, 7]. Intriguingly, this may explain the near absence of GM-IVH after over 3–5 days of birth irrespective of the duration of gestation. Likely, higher oxygenation following birth inhibits rapid angiogenesis. Thus, a labile combination of metabolically active immature/precursor cells with a rich but “structurally weak” vasculature provided a high-risk background for bleeding, especially with high-velocity cerebral blood flow.
Among many factors associated with alteration in cerebral blood flow, severe respiratory distress syndrome, patent ductus arteriosus, high central venous, and hypercarbia are most prominent. While autoregulation maintains constant cerebral blood flow, this mechanism is impaired in premature infants with lower birth weight. Thus, changes in blood volume or pressure are more likely to affect cerebral circulation. Interestingly, the results of studies directly comparing impaired autoregulation with GMH-IVH have been mixed [18, 19, 20] and provide an opportunity for further research in this direction. As seen in pneumothorax and mechanical ventilation (on high mean airway pressure mode), high central venous pressure stands out as a solid contender to contribute to IVH. This is also concordant with the venous nature of GM-IVH [21]. Interestingly, mechanical ventilation in synchronized and intermittent mandatory mode prevents higher velocity/turbulence of cerebral blood than fixed frequency/pressure modes.
Significant other risk factors affecting include prolonged labor, maternal chorioamnionitis, early-onset sepsis, development of respiratory distress, recurrent tracheal suctioning (supportive care especially during mechanical ventilation), and hypoxia. While most of these factors impact cerebral blood flow, infectious and hypoxic etiologies alter the GM microvasculature. The role of hypotension and rapid sodium bicarbonate infusion in the causation of IVH are inconclusive.
Clinical manifestations of GM-IVH include asymptomatic to subtle alterations in consciousness, limb and eye movement, and changes in muscular tone following IVH. Further, severe cases may be associated with cardiorespiratory distress and progression to seizures, hypotonia, or decerebrate posturing [22].
Cranial ultrasound (CUS) remains the most practical and well-utilized approach for diagnosing and monitoring GM-IVH evolution. Newer ultrasound devices with high-frequency transducers allow for enhanced evaluation. Epidemiologically, surviving infants born preterm at 24 weeks have a higher incidence (10–25%) of high-grade GM-IVH (grade 3–4) as compared to preterm infants born after 28 weeks (<5%) [8, 9, 10]. Almost half the cases of postnatal GM-IVH present on the first day of life, with nearly ~90% presenting within the first 72 hours. As discussed in pathogenesis, increased oxygenation after birth likely stabilizes the GM-BBB and makes infants almost resistant to GM-IVH after the first week of life irrespective of gestational age [23]. Therefore, regular CUS schedules have been recommended based on the gestational age at birth and when otherwise clinically indicated [24].
Traditionally, GM-IVH had been graded into four categories based on the extent of hemorrhage beginning in the venule that drains into the subependymal collector veins: grade-1 representing subependymal hemorrhage; grade-2 with limited (filling <50% of normal-sized ventricles) IVH; and grade-3 with extensive IVH. Grade-4 was defined as IVH with parenchymal extension [25]. However, the latter was better identified as parenchymal venous infarction (PVI), though parenchymal extension does also rarely occurs [26]. Interestingly, PVI may occur in all, including lower grades (1 and 2) of GM-IVH [22]. Since PVI is associated with long-term complications and risk of mortality (based on location and extent), a three-stage grading with an additional description of PVI has been recommended [22, 24] (Figure 2). In addition, early GMH may alter local neuronal and glial precursors with neurological consequences, description of location of bleed in addition to grade is suggested.
GMH/IVH: Origin and grading. GMH starts in a venule that drains into lateral subependymal collector veins; it extends into white matter by virtue of venous compression and infarction; bottom row: T2-weighted MRI of GMH with limited IVH and limited venous infarct. (Derived from Parodi et al. [
On CUS, grade 1 GMH is subependymal, hyperechoic, and globular. Evaluation in both coronal and sagittal planes helps distinguish a small GMH from choroid plexus on an initial diagnostic scan. Also, echogenicity at the caudothalamic groove (usual site for GMH) in the late neonatal period likely represents hyperechoic germinolysis and not late GMH [27]. Distinguishing pure subependymal bleed from IVH may be challenging on CUS. Indirect signs of hyperechoic ependymal changes, which usually occur 2 to 4 weeks after IVH, and insonation through mastoid fontanelle are helpful in this distinction [24] and aid prognostication and counseling. Clot changes overtime should also be recorded. A subacute clot or clot remnants early after birth may represent an antenatal hemorrhage.
PVI typically is identified as a triangular echo density in the periventricular white matter adjacent to the GMH. The infarct may not touch the GMH initially and may or may extend into the GMH depending on severity. Infarcts eventually evolve into cavitary lesions, and porencephaly ensues in 1–2 months [24]. This cavitation is asymmetric, unilateral, and permanent in contrast to cysts of periventricular leukomalacia (symmetric, bilateral, and transient) [22].
A quarter of infants with GM-IVH develop posthemorrhagic ventricular dilatation (PHVD) due to imbalanced production and resorption of CSF. This dilatation occurs a few days to weeks after IVH and is followed by subsequent regression [28]. PHVD is more common in higher grades but can occur in all cases with IVH. Thus, serial CUS is recommended in IVH cases until term-equivalent age. While a subset of cases resolves spontaneously, balancing the complications of compression versus those of surgical management (tapping, shunt) remains a challenge [29]. PVHD, as expected, is associated with a poor neurological outcome in the long term.
Thrombophilic genotype is frequently associated with a subset of severe GM-IVH patients with atypical clinical presentation. The atypical presentation includes periventricular hemorrhagic infarction presenting within 6 hours of birth or after four days of birth, in the absence of secondary inciting factors like sepsis. Factor V Leiden mutation was the most common genetic alteration, frequently with mothers being carriers. Prothrombin mutations and polymorphism of the
Mutations of the
Experimental models have shown tropomyosin receptor kinase B (TrkB) to influence the inflammatory status in the microenvironment following GMH by influencing the phosphatidylinositol-3-kinases (PI3K)/protein kinase B (Akt)/forkhead box protein O1 (FoxO1) pathway [35].
Overall, genetic alteration in components of vascular structure, coagulation mechanism, and inflammatory pathways have been described in a subset of GM-IVH. The authors believe that recent progress in inflammation and growing knowledge of inflammasome complex may be employed towards further research in this direction.
Our understanding of IVH due to a structurally labile and immature vasculature in the germinal matrix and alterations in cerebral blood flow in premature infants forms the focus of most strategies to prevent GM-IVH. In principle, delay of preterm birth relies on decreasing GM vascular density with advanced gestational age. Moreover, high postnatal oxygen levels in the infant mediate the stabilization of the GM blood vasculature and ensure freedom from IVH in 3–5 days after birth, highlighting the critical importance of timeliness in management and prevention.
Steroids (glucocorticoids) like dexamethasone and betamethasone are administered to pregnant women in premature labor under 34 wg. Glucocorticoids cause a selective inhibition of blood vessels in the GM- BBB that lack adequate pericyte coverage, inhibit angiogenesis, and subsequently stabilize vasculature [12, 14, 36]. In addition, prenatal corticosteroid assists in development lungs surfactant and protect against respiratory distress syndrome. The latter effect also prevents turbulent cerebral blood flow. Prenatal corticosteroid usage is one of the rare factors that has consistently been associated with a reduction in occurrence and severity of IVH [37, 38].
Indomethacin is a non-selective cyclooxygenase (COX) inhibitor and reduces severe IVH, especially in males [39, 40]. Indomethacin is employed for closure of patent ductus arteriosus that in turn prevents altered cerebral blood flow. It also suppresses angiogenesis by COX-2 inhibition [1]. Although indomethacin can decrease IVH in the short term, its usage is not associated with reducing long-term neurological complications such as cerebral palsy, deafness, and blindness [41, 42, 43]. Hence, indomethacin has limited acceptance and is based on regional preferences.
Prenatal care and transport: It is recommended that pregnant mothers be given adequate antenatal care and those in preterm labor be transported (while pregnant) to tertiary care units better equipped to manage both mother and child. Transportation of extremely premature infants has long been associated with the increased occurrence and severe IVH [44].
It is beneficial to note that antenatal phenobarbital and magnesium, vitamin-K, and fresh frozen plasma did not influence the occurrence of IVH [45, 46, 47, 48, 49].
Intriguing preclinical studies show time-sensitive windows for therapeutic pharmacological targeting of the GM “weakened” BBB by altering the integrin-β8 and TGF-β pathways [50].
Currently, there is a paucity of active treatment strategies for the management of established GM-IVH. Maintaining blood pressure levels and respiratory status, with judicious use of IV fluids, blood transfusions, and respiratory support (if needed), might prevent the progression of hemorrhage. Electroencephalogram (EEG) monitoring should be done in the presence of seizures [3]. Apart from supportive treatment, emphasis is laid on the preservation of cerebral perfusion and the prevention of complications. Monitoring twice weekly with CUS for four weeks (or similar) and then weekly till term equivalent age recommended to evaluate GMH and post hemorrhage hydrocephalus (PHH).
Multiple trials and observational studies have focused on the relative head position of premature infants soon after birth in relation to IVH. These positional strategies focus mainly on maintaining adequate cerebral blood flow.
While previous studies on the effect on neutral head position found no significant association with the occurrence of IVH [51], these studies were also limited by small sample size [52]. More recently, efficient, supportive nursing intervention in premature infants during the first 72 hours of birth has been associated with decreased incidence and progression of GM-IVH [53]. This four-pronged approach includes midline head position, head elevation of the incubator, and slow vascular flushing/withdrawal of blood, and sudden elevation of the legs. First, the head in midline position ensures adequate venous drainage. Head rotation impedes jugular venous outflow on the ipsilateral side and may cause congestion, relative hypoxia and eventually aid GMH [54]. Second, incubator head lift (15–30 degrees) enhances gravitational cerebral venous drainage [55]. Third, sudden elevation of legs, as in to change diapers, may result in increased venous return, increase cardiac preload, thereby altering cerebral perfusion. Finally, avoiding rapid (lasting <30 seconds) vascular flushing/blood collection can avoid a transient though significant alteration in cerebral blood flow [56]. The effect of the intervention was stronger in infants born before 27 wg [53]. While previous studies on the effect on neutral head position found no significant association with the occurrence of IVH [51], these studies were limited by small sample size [52]. A more recent meta-analysis showed the limited utility of supine midline head position for the prevention of GM-IVH. However, midline head position with an elevation of incubator head was associated with lower mortality [57]. Overall, concomitant intervention with neutral head position, the elevation of incubator head, and avoidance of sudden leg elevation and sudden vascular volumetric changes provide evidence for a better outcome.
The survivors of severe GMH frequently develop post-hemorrhagic hydrocephalus (PHH). A subset of these cases requires surgical shunting, which is not without its complications, including infections, obstruction, and displacement [58]. In addition, the cerebroventricular dilatation causes physical pressure on the brain parenchyma and is associated with neurological impairment in the long term. Mechanism of PHH: Obstruction of the cerebral aqueduct, foramina of Luschka and Magendie, and subarachnoid outflow passages by blood clots/microthrombi may cause PHH. Historically, fibrinolytic therapy has not been successful in the management of PHH.
The tissue macrophage system responds to intracranial hemorrhage similar to other locations in the body. Red blood cells (RBCs) are phagocytosed by macrophages (erythrophages), and subsequently, hemoglobin is degraded. Iron mainly converts to coarse, irregular hemosiderin granules and porphyrin rings into bilirubin. In exceptional circumstances with closed compartments and lower oxygen tension, such as intracranial bleed, hematoidin, a crystalline, reduced biliverdin product may be formed. Post hemorrhagic components are frequently encountered on light microscopic evaluation of the cerebrospinal fluid (CSF), as early as 1–2 days after bleeding [59, 60]. In addition to the erythrophagocytosis, cellular components of the ventricular lining (ependymal cells and choroid plexus cells) and rarely, precursor germinal matrix cells (due to close proximity with disrupted ventricular lining) may be identified in CSF analysis [61, 62, 63].
Superficial siderosis (SS) is the deposition of hemosiderin in the subpial layers of CNS, resulting in sensorineural hearing loss and cerebellar ataxia in most adults cases [64]. Susceptibility weighted imaging (SWI), an MRI sequence, identified SS in the ependymal layer, brain stem, cerebellum with vermis, and Sylvian fissures. Interestingly the depth of SS correlated with the increasing grade of GM-IVH. Also, brain stem and cerebellar SS appear to relate more to IVH than cerebellar hemorrhage [65].
A review of scientific literature shows the following current trends exploring the management of GMH and prevention of complications.
Experimental models have shown the role of iron (from red blood cells) to develop brain edema and acute ventricular dilatation [66]. As proof of principle, iron chelation with deferoxamine has showed reduced long term PHH after GMH in neonatal rats [67, 68]. Another group found biliverdin reductase to enhance CD36 expression in scavenging microglia and hematoma resolution through NOS/TLR4 pathway [69]. Additionally, iron overload has been associated with increased aquaporin-4 expression [70]. However, diuretic treatment has not been found to be beneficial.
Along similar lines, “normal appearing” white matter in preterm infants with severe GM-IVH, at term equivalent age, showed paramagnetic (positive magnetic) susceptibility, likely due to diffusion of iron into the periventricular white matter [71]. This radiological finding may be employed as an innovative methodology for future research focusing on the spatial impact of iron deposition on long-term neurological consequences.
Post GMH levels of pro-inflammatory markers like TNFα are elevated. In response to hemorrhage and associated tissue injury, resident microglia are activated in an inflammatory process [72, 73, 74]. Additional experimental models have shown microglial proliferation surrounding the clot with phosphorylated ERK. Minocycline and cannabinoid receptor-2 agonists have also shown promise to curb down inflammation [75]. CD200Fc inhibits inflammation following GMH likely by mediating CD200R1/Dok1 pathway [76]. IVH has been shown to cause a TLR4 and NF-κβ based inflammatory pathway mediated increase in CSF production in the choroid plexus. As a proof of principle, amelioration of these mediators was associated with control of CSF production and improvement in PHH [77]. The role of M2 microglia stimulation through the PPARγ and CD36 scavenger receptor for short-term resolution of hematoma has also shown promising results for further clinical evaluation [78]. NT-4 controls neuroinflammation by interacting with TrkB to induces PI3K-Akt pathway and inhibits downstream FoxO1 in experimental models [35]. These results promise potential for clinical utility in the management of PHH.
Extracellular matrix (ECM), especially components fibronectin and vitronectin, are elevated post-GMH and are hypothesized to deposit (like microthrombi), potentially causing CSF obstruction [75, 79, 80, 81]. TGF-β may be induced by thrombin and promotes the production of ECM, especially TGF-β1 isoform whose levels have been elevated in studies after GMH. It’s inhibition has been associated with attenuated PHH and neurological decline [75, 81]. While GFAP expression is markedly increased in experimental IVH models, umbilical cord mesenchymal stem cell infusion has been associated with a decline in GFAP expression and subsequent PHH development [82]. The role of GFAP and astrocytes in gliosis post IVH requires further attention. More recently, astrogliosis was associated with redistribution of aquaporin-4 and altered CSF dynamics. Olomoucine controlled scarring and attenuated PHH by inhibition of cyclin-dependent kinase (CDK) [83]. Secukinumab, monoclonal IgG1κ targeting IL17a, is protective against reactive astrogliosis following GMH, partly by regulating IL-17RA/(C/EBPβ)/SIRT1 pathways [84].
While neurological complications in survivors of high-grade GM-IVH are well documented, the impact of low-grade IVH currently continues to be better understood. Low-grade IVH was associated with moderate to severe neurodevelopmental impairment (NDI) and without association with cerebral palsy [85]. A case-controlled retrospective study using CUS found no significant impact of low-grade GM-IVH on neurological complications of cerebral palsy and neurodevelopmental delay evaluated during 18–30 months after birth [86]. Both these studies were limited in power and in analysis by more sensitive MR-based techniques [87]. A more recent MR-based study has revealed microstructural impairment of white matter related to neurodevelopmental impairment at 24 months in early GMH [88]. Similarly, magnetic resonance with 3D pseudo-continuous arterial spin-labeling (pCASL) perfusion sequence-based study has shown consistently lower CBF in the posterior cortical and subcortical gray matter regions in preterm neonates with low grade IVH [89]. This regional susceptibility also requires correlation with long term studies. From a developmental perspective, neurological alterations are not incompatible with low-grade IVH. GMH may lead to altered myelination in the white matter since ganglionic eminence is the seat of oligodendroglial precursor cells that migrate to cerebral white matter areas to produce myelin later in the third trimester [90]. Besides, GM is involved in the development of GABAergic interneurons significant for high-level cognitive function [91].
Germinal matrix intraventricular hemorrhage is the most common intracranial hemorrhage in newborns, particularly preterm neonates. Improvements in obstetric and neonatal care have led to increased survival of preterm infants. Despite extensive research and preventive measures, the incidence of associated complications and mortality remains high. The GM is highly susceptible to hemorrhage due to a combination of delicate vasculature and fluctuations of cerebral perfusion, uncontrolled by autoregulatory mechanisms. Genetic factors and coagulation disorders may factor in if present. Obstetric and neonatal clinicians should use the available knowledge to prevent the occurrence of and progressions of hemorrhages. Therapeutic options for the management of GM-IVH are predominantly limited to supportive care and monitoring. Shunts have proven to be effective in challenging cases of PHH. Current and ongoing improvement in the molecular understanding of GM-IVH and its complications using multi-omics investigations is essential to develop biomarkers and therapeutic strategies.
The authors thank Mr. Fredrik Skarstedt for his immense support with digital image preparation.
The authors declare no conflict of interest.
We are living in a world of many challenges such as climate changes, polluted environment, resource depletion, and increasing demand for fuel. The use of oil reserves to fulfill our need of fuel has caused many drastic challenges from energy security to change in temperature. Rapid industrialization has increased the demand of petroleum products and consequently has raised the monopoly of few countries, which can manipulate petroleum price and create instability. This may also create environmental problems by emission of greenhouse gases and subsequently effect on climate change. The most important source of energy is petroleum that is largely used in transportation and industries; therefore, viability of liquid fuel is enhanced. As the environmental issues are growing, more research is being conducted to address the problems. The search for alternative source of petrol that is less costly with minimal environmental effects has become the center of attention. For instance, biomass is considered as a sustainable resource that can be utilized in large-scale production of biofuel that can be utilized as an alternative source of fuel and may present solution to environmental problems. Furthermore, relying on fossil fuel could be detrimental as it has been predicted of its depletion by 2050. The total annual primary production of biomass is over 100 billion tonnes of carbon per year, and the energy reserve per metric tonne of biomass is between 1.5E3 and 3E3 kW hours that is sufficient to cater the needs of the world energy requirements [1].
\nBioenergy products like bioethanol, biohydrogen, and biodiesel can be obtained from lignocellulose biomass which is considerably large renewable bioresource and obtained from plants. The term “lignocellulosic biomass” is defined as lignin, cellulose, and hemicellulose that constitute the plant cell wall. Strong cross-linking associations are present between these components that cause hindrance in the breakdown of plant cell wall. Polysaccharides and lignin are cross-linked via ester and ether linkages [2, 3, 4]. Microfibrils that are formed by cellulose, hemicellulose, and lignin help in the stability of plant cell wall structure [5, 6].
\nLignocellulose was first produced from food crop such as corn, oilseed, and sugarcane. But the use of edible feedstock for bioenergy products formation is being discouraged to prevent the rise in food competition. Thus, second-generation biofuels are obtained from plants wastes to avoid competition of land and water resources between energy crops and food crops. Currently, lignocellulose is being produced from wood residues, agricultural residues, food industry residue, grasses, domestic wastes, municipal solid wastes, and nonfood seeds [7, 8, 9]. The lignocellulose wastes (LCW) are largest renewable bioresource reservoir on earth that is being wasted as pre and postharvest agricultural wastes. Thus, many steps need to be adopted for use of these renewable resources for the production of bioenergy products. Recovery of many products like enzymes, methane, activated carbon, lipids, resins, methane, carbohydrates, surfactants, resins, organic acids, ethanol, amino acids, degradable plastic composites, biosorbents, biopesticides, and biopromoters can be achieved by utilizing LCW. The added benefits of using LCW besides recovery of different products are the removal of LCW waste from the environment. Also, utilization of LCW eliminates the use of food for bioethanol production. The US government has planned the production of 21 billion gallon of biofuels by 2022 [2, 5]. Biofuel production from lignocellulosic biomass reduces the emission of greenhouse gases.
\nPretreatment brings physical, biological, and chemical changes to biomass structure; therefore, it is very important to consider the type of pretreatment. In order to break down the hindrance caused by strong association within the cell wall, pretreatment is an important step which can increase the availability of lignocellulosic biomass for cellulase enzymes, their digestibility, and product yield. Before subjection to enzymatic hydrolysis, pretreatment of biomass can increase the rate of hydrolysis by 3–10-fold. Pretreatment of LCW is not an easy step as it seems after the installation of power generator; pretreatment is the second most costly process at industrial level. In crystalline cellulose, the disruption of hydrogen bonds, cross-linked matrix disruption, and increase in porosity as well as surface area of cellulose are the three tasks that are performed via a suitable pretreatment methods. The outcome of pretreatment also differs due to the difference in the ratio of cell wall components [10, 11]. The option to use dilute acid pretreatment method is more effective against poplar tree bark or corn as compared to the same method used for sweet gum bark or cornstalks. Few requirements of an effective, efficient, and economically suitable pretreatment process that including use of cheap chemicals, very less consumption of chemicals, prevention of hemicellulose and cellulose from denaturation, minimal energy requirement and consumption, cost-effective size reduction process, and reactive cellulosic fiber production are the factors that need to be considered for pretreatment. There are several methods of pretreatment that can be divided into four categories, namely, chemical, physical, biological, and physiochemical pretreatment [12, 13, 14, 15].
\nPore size and surface area of lignocellulosic biomass can be increased, whereas crystallinity and degree of polymerization of cellulose can be decreased with the application of physical methods. Physical pretreatments include milling, sonication, mechanical extrusion, ozonolysis, and pyrolysis.
\nOn the inherent ultrastructure of cellulose and degree of crystallinity, milling can be performed to render lignocelluloses more amenable to cellulases. Cellulases are enzyme that catalyze cellulose, but for the catalysis and best results, the substrate availability needs to be enhanced for optimized functioning of the enzymes. Before the subjection of the LCW to enzymatic hydrolysis, milling and size reduction of the lignocellulosic matter should be performed. Milling process has several types like ball milling, colloid milling, vibro-energy milling, hammer milling, and two-roll milling. For wet material, colloid mill, dissolver, and fibrillator are suitable, whereas for dry materials hammer mill, extruder, cryogenic mill, and roller mill are used. For both wet and dry material, ball milling can be used. For waster paper, hammer milling is the most suitable pretreatment option. Enzymatic degradation can be improved by milling as it reduces the degree of crystallinity and material size. Up to 0.2 mm reduction in particle size can be seen by milling and grinding. Reduction in particle size of biomass can be achieved up to a certain limit; beyond that limit reduction in particle size does not effect in the pretreatment procedure. Corn stover with small particle size, i.e., from 53 to 75 μm, is more productive as compared to large particle size corn stover ranging from 475 to 710 μm. The difference in particle size shows that productivity can significantly affect the pretreatment process. Ball milling causes a massive drop in crystallinity index from 4.9 to 74.2% which makes this process more suitable for saccharification of straw at mild hydrolytic conditions with more production of fermentable sugars [12, 16, 17, 18]. For better results of hydrolysis, milling can be used in combination with enzymatic hydrolysis. Mechanical action, mass transfer, and enzymatic hydrolysis can be achieved at the same time when two methods are combined. A number of ball beads in bill mill reactor play a crucial role in the α-cellulose hydrolysis, as less enzyme loading is required, and 100% rate of hydrolysis can be achieved in comparison to pretreatment of biomass that is carried without the use of milling procedure. Highest hydrolysis rate with high yield of reducing sugar was obtained when rice straw was put into fluidized bed opposed jet mill for fine grinding after cutting, steam explosion, and pulverization. For pretreatment of biomass, ball milling is an expensive option in terms of energy consumption, which is a huge disadvantage at industrial scale. Also, incapability of milling for removing lignin makes it a less suitable option as enzyme accessibility to the substrate is reduced in the presence of lignin. Reduction in crystallinity, degree of polymerization, and increase in surface area can be effected by the type of biomass, type of milling used for pretreatment, and duration of the milling process [19, 20, 21].
\nFor improving digestibility and reducing crystallinity, vibratory ball milling is very effective. Low energy consumption has an important advantage of using wet disk milling which produces fibers that improve hydrolysis of cellulose, whereas hammer milling produces finer bundles. Due to this reason milling is not preferred when wet disk milling is available [22, 23]. Other study results of conventional ball and disk milling are compared. With the use of conventional ball milling, maximum yields of xylose and glucose were obtained, i.e., 54.3 and 89.4%, respectively [24]. Wet milling produces less yield, but it has the advantage of not producing inhibitors and very low energy consuming capability. An increase of 110% in enzymatic hydrolysis was achieved when wet milling was combined with alkaline pretreatment. Optimum parameters for wet milling pretreatment of corn stover were 10 mm diameter 20 steel balls, 1:10 solid-to-liquid ratio, 350 rpm/min speed, and 0.5 mm particle size [25] (Figures 1 and 2).
\nColloid milling (
Hammer milling (
Commonly used method for plant biomass pretreatment is microwave irradiation. This pretreatment method has several advantages that include ease of pretreatment, increased heating capacity, short processing time, minimal generation of inhibitors, and less energy requirement. Microwave irradiation in closed container was first reported in 1984 by team of researchers from Kyoto University, Japan. They treated sugarcane bagasse, rice straw, and rice hulls with microwaves in the presence of water. The conditions used for microwave treatment include glass vessels of 50 mL, 2450 MHz energy, and 2.4 kW microwave irradiation [26]. Classical pretreatment methods were carried out at high pressure and temperatures. Chemical interactions between lignocellulosic material break as a result of high temperature, thus increasing substrate availability to the enzymes. Under high-pressure steam injection or indirect heat injection, high temperature between 160 and 250°C is provided to lignocellulosic material in conventional heating methods. However, in order to prevent temperature gradients, crushing of lignocellulosic material into small particles is needed. To avoid large temperature gradients, microwave is a good choice as it uniformly distributes heat which also avoids degradation of lignocellulosic material into humic acid and furfural. For effective degradation, microwave irradiation is combined with mild alkali treatment. Sugar yield of 70–90% from switch grass was obtained from alkali and irradiation combined pretreatment [27]. As microwave irradiation is performed at high temperature, therefore, closed containers are required to achieve high temperature. Three properties, namely, penetration, reflection, and absorbance are exhibited by microwave. Microwave passes through glass and plastic, absorbed by water and biomass, whereas microwaves are reflected by metals. Based on these properties, microwave reactors can be divided into two types, one that allows the passage of microwaves, whereas the other kind reflects the microwaves. Glass or plastic is the building material of the first type of microwave reactors, whereas the second types of reactors are composed of steel. Through quartz windows, microwaves can enter into the reactor as these are placed in the reactor. Closed, sealable, pressure-resistant glass tube container having gasket made up of Teflon can be used for the high temperature, i.e., 200°C, for microwave irradiation pretreatment. Sensors are used to control and ensure temperature inside the microwave. Teflon-coated sensors are a good choice because of the thermostability, corrosion-free nature, and zero absorbance properties. In a microwave oven, Teflon vessels are used by some scientists due to its advantageous properties [28, 29]. Normally vessel sizes vary from 100 mL to several hundred milliliters. A 650 mL vessel with 318 mm length, connected nitrogen bottle, gauges, and thermometers are installed on the top of the microwave that was designed by Chen and Cheng [30]. Besides the glass vessels and stainless steel tanks with temperature and pressure sensors, automatic controlling system for microwave input and mechanical stirrer are also used (Figure 3).
\nMicrowave irradiation (
When materials that can pass through a defined cross section die, it appears out with the fixed definite profile. This is the extrusion process which is known for sugar recovery from biomass. Adaptability to modifications, no degradation products, controllable environment, and high throughput are few advantages related to mechanical extrusion pretreatment process. Single screw extruder and twin screw extruder are two types of extruders.
\nSingle screw extruder is based on three screw elements, forward, kneading, and reverse. With the minimum shearing and mixing, bulk material of varying pitches and lengths can be transported by forward screw element. Prominent mixing and shearing effect is produced by kneading screw elements with weak forward conveying effect, whereas the use of immense mixing and shearing involves material that is pushed back by reverse screw elements. A screw configuration is defined by the arrangement of different stagger angels, lengths spacing, pitches, and positions. Twin screw extruder can accomplish multiple tasks at the same time like mixing, shearing, grinding, reaction, drying, and separation. High enzymatic hydrolysis rates are achieved by the use of single and twin screw extruders. Different parameters like speed of screw, temperature of barrel, and compression ratio can significantly affect recovery of sugars. Short-time extruders provide fast heat transfer, proper mixing, and increased shear. When material passed through the extruder barrel, structure of biomass is disturbed, exposing more surface for enzymatic hydrolysis [31, 32, 33]. During extrusion process, lignocellulosic material can be treated with alkali or acid in order to increase sugar recovery. Acidic treatment is less preferred than alkali because of the corrosion caused by acid to the extruder material. Corrosion problem can be solved by the use of AL6XN alloy for barrel fabrication and screws of extruder. With less carbohydrate degradation and role in the delignification, alkali treatment is suitable for lignocellulosic material. Sodium hydroxide is most commonly used to break ester linkages and solubilization of lignins and hemicelluloses. Alkali treatment can be applied by addition of alkali using volumetric pump into the extruder or by soaking the lignocellulosic material in alkali at room temperature [31, 34, 35] (Figure 4).
\nTwin screw extruder (
For the production of bio oil from biomass, process of pyrolysis is used. Pyrolysis is a thermal degradation of lignocellulosic biomass at very high temperature without the presence of oxidizing agent. At temperature ranging between 500 and 800°C, pyrolysis was performed. Rapid decomposition of cellulose resulted in the formation of products like pyrolysis oil and charcoal [36]. Based on temperature, pyrolysis pretreatment process is divided into fast and low pyrolysis. Certain factors affect the end products like biomass characteristics, reaction parameters, and type of pyrolysis. Due to high-value energy-rich product formation, easy transport management retrofitting, combustion, storage, and flexibility in utilization and marketing, thermal industries are adapting to the process of pyrolysis. Presence of oxygen and less temperature increase the efficiency of this process. A study on the bond cleavage rate of cellulose was carried out in the presence of nitrogen and oxygen. During the process of pyrolysis, breakage of 7.8 × 109 bonds/min/g cellulose in the presence of oxygen and breakdown of 1.7 × 108 bonds/min/g cellulose in the presence of nitrogen at 25°C were observed. In order to obtain more efficiency and results, microwave-assisted pyrolysis is preferred due to the microwave dielectric heating [37]. Thermochemical conversion of biomass into biofuels can be performed via three technologies, gasification, pyrolysis, and direct combustion [38]. Different yields of products from pyrolysis are due to different modes of pyrolysis. Bio oil is a mixture of polar organics and water. Pyrolysis is used where bio oil production is required. Fast pyrolysis in a controlled environment leads to the formation of liquid products (fuels). Torrefaction is an emerging technique which is also known as mild pyrolysis. It differs from pyrolysis with reference to thermochemical process that is carried out at temperature range between 200 and 300°C. Partial decomposition of biomass occurs in this process, and ultimate product obtained is terrified biomass. Whereas, in the process of pyrolysis, plant biomass is decomposed into vapor, aerosols, and char. Torrefaction has been categorized into two categories based on dry and wet torrefaction.
\nDry torrefaction needs an inert environment and completely dry biomass and normal atmospheric pressure. Biochar is the major product in this type of biomass pretreatment. Hydrothermal carbonization and hydrothermal torrefaction are other terminologies used for wet torrefaction. Unlike dry torrefaction, pressurized vessel of water is used to carry out the pretreatment. Biomass used for wet torrefaction contains moisture content, but after torrefaction, a drying process is necessary in this type of torrefaction. A pressure between 1 and 250 MPa is required to carry out wet torrefaction. Biomass used during wet torrefaction pretreatment produces hydro-char as a main product [39].
\nIn this method, pores are created in the cell membrane due to which cellulose exposes to such agents that cause its breakdown by entering into the cell. High voltage ranging between 5.0 and 20.0 kV/cm is applied in a sudden burst to biomass for nano- to milliseconds. Sample was placed between two parallel plate electrodes, and the strength of electric field is given as
Pulse electric field (
In this pretreatment, acids are used to pretreat lignocellulosic biomass. The generation of inhibitory products in the acid pretreatment renders it less attractive for pretreatment option. Furfurals, aldehydes, 5-hydroxymethylfurfural, and phenolic acids are the inhibitory compounds that are generated in huge amount in acid pretreatment. There are two types of acid treatments based on the type of end application. One treatment type is of short duration, i.e., 1–5 min, but high temperature > 180°C is used, and the second treatment type is of long duration, i.e., 30–90 min, and low temperature < 120°C is utilized. Due to hydrolysis by acid treatment, separate step of hydrolysis of biomass can be skipped, but to remove acid, washing is required before the fermentation of sugars [43, 47]. For acid pretreatment, such reactors are required that show resistance to corrosive, hazardous, and toxic acids; therefore, acid pretreatment is very expensive. Flow through, percolation, shrinking-bed, counter current rector, batch, plug flow are different types of rectors that have been developed. For enhancing economic feasibility of acid pretreatment, recovery of concentrated acid at the end of the treatment is an important step.
\nTo treat lignocellulosic biomass, concentrated acids are also used. Most commonly used acids are sulfuric acid or hydrochloric acid. In order to improve the process of hydrolysis for releasing fermentable sugars from lignocellulosic biomass, acid pretreatment can be given. For poplar, switch grass, spruce, and corn stover, sulfuric acid pretreatment is commonly used. Reducing sugars of 19.71 and 22.93% were produced as a result of the acid pretreatment of Bermuda grass and rye, respectively. In percolation reactor, pretreatment of rice straw was carried out in two stages using aqueous ammonia and dilute sulfuric acid. When ammonia is used, 96.9% reducing sugar yield was obtained, while 90.8% yield was obtained in case of utilization of dilute acid.
Besides sulfuric acid and hydrochloric acid, other acids like oxalic acid and maleic acid are also used for the pretreatment of lignocellulosic biomass. Oxalic and maleic acids have high pKa value and solution pH as compared to sulfuric acid. Because of having two pKa values, dicarboxylic acids hydrolyze biomass more efficiently than sulfuric acid and hydrochloric acid. Other advantages include less toxicity to yeast, no odor, more range of pH and temperature for hydrolysis, and no hampering of glycolysis. Maleic acid has khyd/kdeg, due to which hydrolysis of cellulose to glucose is preferred over glucose breakdown. Effects of oxalic, sulfuric, and maleic acid pretreatment on biomass at the same combined severity factor (CSF) were determined [53]. The use of maleic acid produces high concentration of xylose and glucose as compared to oxalic acid.
\nApart from acids, few bases are also used for pretreatment of biomass. Lignin contents greatly affected the result of alkaline treatment. As compared to other pretreatment methods, alkali treatment requires less pressure and temperature and ambient condition, but alkali pretreatment needs time in days and hours. Degradation of sugar in alkali treatment is less than that by acid treatment, and also the removal and recovery of caustic salt are possible and easy in case of alkali treatment. Ammonium, sodium, calcium, and potassium hydroxides are used for alkaline pretreatment, but among these sodium hydroxide is the most commonly used alkaline pretreatment agent, whereas calcium hydroxide is the cheapest yet effective among all other alkali agents for pretreatment. By neutralizing calcium with carbon dioxide, calcium can be recovered easily in form of insoluble calcium carbonate. Using lime kiln technology, calcium hydroxide can be regenerated. Apparatus required for alkali pretreatment is basically temperature controller, a tank, CO2 scrubber, water jacket, manifold for water and air, pump, tray, frame, temperature sensor, and heating element. The first step of pretreatment consists of making lime slurry with water. The next step is spraying of this slurried lime on biomass; after spray, store the biomass for hours or, in some case, days. Contact time can be reduced by increasing temperature [54, 55, 56, 57]. Crystallinity index increases in lime pretreatment because of the removal of lignin and hemicellulose. Structural features resulting from lime pretreatment affect the hydrolysis of pretreated biomass. Correlation of three structural factors, viz., lignin, acetyl content and crystallinity, and enzymatic digestibility, was reported by Chang and Holtzapple [58]. He concluded that (1) regardless of crystallinity and acetyl content, in order to obtain high digestibility, extensive delignification is enough. (2) Parallel barriers to hydrolysis are removed by delignification and deacetylation. (3) Crystallinity does not affect ultimate sugar yield; however, it plays some role in initial hydrolysis. It is evident from these points that lignin content should be reduced to 10% and all acetyl groups should be removed by an effective pretreatment process. Thus in exposing cellulose to enzymes, alkaline pretreatment plays an important role. By increasing enzyme access to cellulose and hemicellulose and eliminating nonproductive adsorption sites, lignin removal can play its role in increasing effectiveness of enzyme.
\nAqueous organic solvents like methanol, acetone, ethanol, and ethylene glycol are used in this method with specific conditions of temperature and pressure. Organosolv pretreatment is usually performed in the presence of salt catalyst, acid, and base. The biomass type and catalyst involved decide the temperature of pretreatment, and it can go up to 200°C. Lignin is a valuable product, and to extract lignin this process is used mainly. Cellulose fibers are exposed when lignin is removed, which leads to more hydrolysis. During organosolv pretreatment, fractions and syrup of cellulose and hemicellulose, respectively, are also produced. There are certain variable factors like catalyst type, temperature, and concentration of solvent and reaction time which affects the characteristics of pretreated biomass like crystallinity, fiber length, and degree of polymerization. Inhibitor formation is triggered by long reaction, high temperature, and acid concentrations [59, 60]. In a study by Park et al. [61], effect of different catalyst was checked for the production of ethanol and among sulfuric acid, sodium hydroxide, and magnesium sulfate, and sulfuric acid was found to be most effective in ethanol production, but for enhancing digestibility the use of sodium hydroxide is proven to be effective. Sulfuric acid is a good catalyst, but its toxicity and inhibitory nature make it less favorite. Organosolv is not a cost-effective pretreatment process because of the high cost of catalysts, but it can be made cost-effective by recovering and recycling of solvents. Solvent removal is important because its presence effects fermentation, microorganism growth, and enzymatic hydrolysis. There is added risk of handling such harsh organic solvents. Acid helps in hydrolysis and depolymerization of lignin. Upon cooling lignin is dissolved in phenol, and in the aqueous phase, sugars are present. Formasolv involving formic acid, H2O, and hydrochloric acid is a type of organosolv in which lignin is soluble and at low temperature process can be carried out. For pretreatment with ethanosolv cellulose, hemicellulose and pure lignin can be recovered, but high pressure and temperatures are required when ethanosolv is used, and less toxic nature of ethanol as compared to other organosolv makes it favorite for pretreatment. Ethanosolv when used in pretreatment effects the enzymatic hydrolysis, so to prevent this low ethanol, water is used [62]. Recovery of ethanol and water reduces the overall cost of the pretreatment. For sugarcane bagasse Mesa et al. [63] used ethanosolv at 195°C for 60 min, and results showed formation of 29.1% sugars from 30% ethanol. Alcohol-based organosolv pretreatment is combined with ball milling by Hideno et al. [24] to pretreat Japanese cypress and observed a synergistic effect on digestibility. 50.1, 41.7, and 48.1% yield of organosolv pulping was obtained from ethylene glycol-water, acetic acid-water, and ethanol-water in a study done by Ichwan and Son [64]. Poplar wood chips were first treated with stream and then with organosolv to separate cellulose, lignin, and hemicellulose. About 88% hydrolysis of cellulose to glucose, 98% recovery of cellulose, and 66% increase in lignin extraction were reported by Panagiotopoulos et al. [65].
\nFor the pretreatment of lignocellulose, scientist took a great interest in using ionic liquids, for decades. Ionic liquids containing cations or anions are a new class of solvents with high thermal stability and polarity, less melting point, and negligible vapor pressure [66, 67]. Normally large organic cations and small inorganic anions compose ionic liquids. Factors like degree of anion charge delocalization and cation structure significantly effect physical, biological, and chemical ionic liquid properties. Interactions between ionic liquids and biomass get affected by temperature, cations and anions, and time of pretreatment.
\nIonic liquids actually compete for hydrogen bonding with lignocellulosic components, and in this competition disruption of network occurs. 1-Ethyl-3-methylimidazolium diethyl phosphate-acetate, 1-butyl-3-methylimidazolium-acetate, cholinium amino acids, cholinium acetate, 1-ethyl-3-methylimidazolium diethyl phosphate-acetate, 1-allyl-3-methylimidazolium chloride, and chloride are ionic liquids used for the treatment of rice husk, water hyacinth, rice straw, kenaf powder, poplar wood, wheat straw, and pine. Among other ionic liquids are imidazolium salts which are most commonly used [42]. 1-Butyl-3-methylimidazolium chloride is used for pretreatment by Dadi et al. [68] who observed a twofold increase in yield and rate of hydrolysis. For the pretreatment of rice straw, Liu and Chen [69] used 1-butyl-3-methylimidazolium chloride also known as (Bmim-Cl) and observed significant enhancement in the process of hydrolysis due to modifications in the structure of wheat straw by Bmim-Cl. Bmim-Cl played role in the reduction of polymerization and crystallinity. A twofold increase in hydrolysis yield from sugarcane bagasse was observed in a study by Kuo and Lee [70] as compared to untreated bagasse. 1-Ethyl-3-methylimidazolium-acetate is used in a study by Li et al. [71] for the pretreatment of switch grass in order to remove lignin at a temperature of 160°C for 3 hours. Results showed 62.9% lignin removal enhanced enzymatic digestibility, and reduced cellulose crystallinity was reported by Tan et al. [72] on palm tree pretreatment with 1-butyl-3-methylimidazolium chloride. Slight changes in composition of biomass occurred after ionic liquid pretreatments although significant changes were observed in the structure of biomass. Ionic liquid pretreatment is less preferred over other techniques because of high thermal and chemical stability, less dangerous conditions for processing, low vapor pressure of solvents, and retaining liquid state at wide range of temperature. Ionic liquids can be recycled easily and are non-derivatizing. Disadvantage of using ionic liquid pretreatment is that noncompatibility of cellulase and ionic liquids results in the unfolding and inactivation of cellulase. At less viscosity cellulose solubilizes at low temperature; that’s why while using ionic liquids, viscosity is an important factor to be considered regarding the energy consumption of the whole process. High temperatures trigger more side reactions and negative side effects like reducing ionic liquid stability [73].
\nOzone pretreatment is a great option for lignin content reduction in lignocellulosic biomass. In vitro digestibility of biomass is enhanced by the application of ozone pretreatment. Inhibitors are not formed in this pretreatment which is a great advantage because other chemical pretreatments produce toxic residues. In ozone pretreatment, ozone acts as an oxidant in order to break down lignin. Ozone gas is soluble in water and being a powerful oxidant, by breaking down lignin, releases less molecular weight, soluble compounds. Wheat straw, bagasse, cotton straw, green hay, poplar sawdust, peanut, and pine can be pretreated with ozone in order to degrade lignin and hemicellulose; however, only slight changes occur in hemicellulose, whereas almost no changes occur in cellulose. Ozonolysis apparatus consists of ozone catalytic destroyer, iodine trap used for testing efficiency of catalyst, oxygen cylinder, ozone generator, three-way valve, ozone UV spectrophotometer, pressure regulation valve, process gas humidifier, vent, and automatic gas flow control valve [40, 41, 74, 75, 76]. Moisture content hugely effects oxidization of lignin via ozone pretreatment as lignin oxidation decreases with increase in the moisture content of biomass. Ozone mass transfer is limited at less water concentration, which ultimately effects its reactivity with biomass. Longer residence time of ozone is caused by the blockage of pores by water film [77]. During ozonolysis, pH of water decreases because of the formation of organic acids. Alkaline media trigger delignification because it removes lignins that are bonded to carbohydrates [78, 79].
\nBiomass delignification is associated with the production of inhibitory compounds. Certain aromatic and polyaromatic compounds are produced as a result of delignification [80]. Structural changes in lignin are observed by Bule et al. [81] in a study; different lignin subunits showed aromatic opening and degradation of β-O-4 moieties in NMR analysis. How do aromatic structures of control- and ozone-pretreated samples differ? A spectrum showed a decrease in aromatic carbon signal concentration. Changes were observed in methoxy groups that suggest the breakdown of ester-linked structure. Different reactor designs are used for the ozone pretreatment of biomass, for example, batch reactor, Drechsel trap reactor, fixed bed reactor, rotatory bed reactor, and multilayer fixed bed reactor. Plug flow reactors are used by most researchers [82]. Heiske et al. [83] compared the characteristics of single layered and multiple layered bed reactors in order to improve the wheat straw conversion to methane. Straw with 16.2% lignin concentration was obtained from single layered reactor, whereas in multiple layered reactor, lignin concentration decreased up to 7.2% at the bottom layer. Due to wax degradation in ozone-pretreated wheat straw, production of fatty acid compounds is observed by Kádár et al. [84]. About 49% lignin degradation was observed when corn stover was pretreated with ozonolysis in a study by Williams [85].
\nAFEX technique belongs to the category of physicochemical pretreatment methods. In this low temperature process, concentrated ammonia (0.3–2 kg ammonia/kg of dry weight) is used as a catalyst. Ammonia is added to biomass in a reactor of high pressure; after 5–45 min of cooking, pressure is released rapidly. Normally temperature around 90°C is used in this process. Ammonia can be recovered and reused because of its volatility. The principle of AFEX is similar to steam explosion. Apparatus for AFEX includes reactor, thermocouple well, pressure gauge, pressure relief valve, needle valve, sample cylinder, temperature monitor, and vent. Rate of fermentation is seen to be improved by AFEX pretreatment of various grasses and herbaceous crops. For treatment of alfalfa, wheat chaff and wheat straw AFEX technology is used. Hemicellulose and lignin cannot be removed by using AFEX technology; hence, small amount of material is solubilized only. Degradation of hemicellulose into oligomeric sugars and deacetylation occur during AFEX pretreatment which is the reason of hemicellulose insolubility. After AFEX pretreatment of Bermuda grass and bagasse, 90% hydrolysis of cellulose and hemicellulose was achieved. Effectiveness of AFEX pretreatment decreases with increase in the lignin content of biomass, for example, newspaper, woods, nutshells, and aspen chips. In case of AFEX pretreatment for newspaper and aspen chips, maximum hydrolysis yield was 40% and 50%, respectively. So for the treatment of biomass with high lignin content, AFEX pretreatment is not a suitable choice.
\nAmmonia recycle percolation (ARP) is another method that uses ammonia. Aqueous ammonia (10–15 wt %) is used in this method. With a fluid velocity of 1 cm/min and temperature of 150–170°C and residence time of 14 minutes, aqueous ammonia passes through biomass in this pretreatment, and ammonia is recovered afterwards. Under these conditions, ammonia reacts with lignin and causes the breakdown of lignin breakdown linkages. Liquid ammonia is used in AFEX technique whereas in ammonia recycle percolation method/technique, aqueous ammonia is used.
\nIn this method, high-pressure saturated steam is used to treat lignocellulosic biomass, and then suddenly pressure is reduced, due to which lignocellulosic biomass undergoes explosive decompression. Initiation temperature of steam explosion 160–260°C and 0.69–4.83 MPa pressure is provided for few seconds to minutes, and then lignocellulosic biomass is exposed and retained at atmospheric pressure for a period of time; this triggers hydrolysis of hemicellulose and at the end explosive decompression, terminated the whole process. Cellulose hydrolysis potential increases due to the cellulose degradation and lignin transformation caused by high temperature. During the steam explosion pretreatment, acid and other acids formed, which played their role in the hydrolysis of hemicellulose. Fragmentation of lignocellulosic material occurs due to turbulent material flow and rapid flashing of material to atmospheric pressure [86, 87, 88]. In steam explosion pretreatment, the use of sulfuric acid or carbon dioxide decreases time, temperature, and formation of inhibitory products and increases hydrolysis efficiency that ultimately leads to complete removal of hemicellulose. Steam explosion pretreatment is not that effective for pretreating soft woods; however, acid catalyst addition during the process is a prerequisite to make the substrate accessible to hydrolytic enzymes. By using steam, targeted temperature can be achieved to process the biomass without the need of excessive dilution. Sudden release of pressure quenches the whole process at the end and also lowers the temperature. Particulate structure of biomass gets opened by rapid thermal expansion which is used to terminate the reaction. Steam explosion gets affected by certain factors like moisture content, residence time, chip size, and temperature. By two ways optimal hydrolysis and solubilization of hemicellulose can be achieved; either use high temperature and short residence time or low temperature and high residence time. Low energy requirement is a great advantage of steam explosion pretreatment, whereas in mechanical pretreatment 70% more energy is required as compared to steam explosion pretreatment in order to obtain the same, reduced particle size. So far steam explosion pretreatment with addition of a catalyst is tested and came closest to scaling up at commercial level due to its cost-effectiveness. In Canada, at Iogen demonstration plant, steam explosion pretreatment is used at a pilot scale. For hardwood and agriculture residues, steam explosion pretreatment is a very effective pretreatment process.
\nSupercritical carbon dioxide explosion treatment falls in the category of physiochemical pretreatment. Scientists had tried to develop a process cheaper than ammonia fiber explosion and a process which would operate at temperature lower than stream explosion temperature. In this process, supercritical carbon dioxide is used that behaves like a solvent. Supercritical fluids are compressed at room temperature above its critical point. When carbon dioxide is dissolved in water, carbonic acid is formed which causes less corrosiveness due to its special features. During the process, carbon dioxide molecules enter into small pores of lignocellulosic biomass due to its small size. Carbon dioxide pretreatment is operated at low temperature which helped in prevention of sugar decomposition by acid. Cellulosic structure is disrupted when carbon dioxide pressure is released which ultimately increased the accessibility of the substrate to the cellulolytic enzymes for the process of hydrolysis [11, 40, 41, 43]. Dale and Moreira [89] used carbon dioxide pretreatment for alfalfa and observed 75% theoretical release of glucose. Zheng et al. [90] performed experiments to show comparison among ammonia explosion, steam pretreatment, and carbon dioxide pretreatment of recycled paper and sugarcane bagasse. The results showed that carbon dioxide explosion pretreatment is cost-effective than AFEX.
\nHot compressed water is another terminology used for this method of treatment. High temperature (160–220°C) and pressure (up to 5 MPa) are used in this type of pretreatment in order to maintain the liquid state of water. However, chemicals and catalysts are not used in liquid hot water pretreatment method [42]. In this method, water in liquid form remains in contact with lignocellulosic biomass for about 15 min. In this treatment pressure is used to prevent its evaporation, and sudden decompression or expansion in this pretreatment process is not needed. This method has proved to be very effective on sugarcane bagasse, wheat and rye straw, corncobs, and corn stover. Different terms like solvolysis, aqueous fractionation, aquasolv, and hydrothermolysis are used by different researchers to describe this pretreatment method [42, 60, 91]. Based on biomass flow direction and water flow direction into reactor, liquid hot water pretreatment can be performed in three different ways. The first method is co-current pretreatment, which is carried out by heating biomass slurry and water at high temperature, holding it for a controlled residence time at pretreatment conditions, and finally applying cool environment. The second method involves the countercurrent pretreatment that engages pumping of hot water against biomass at controlled conditions. The third method is the flow-through pretreatment, which can be carried out by the flow of hot water through lignocellulosic biomass which acts like a stationary bed.
\nTo investigate the effect of liquid hot water pretreatment, a study was conducted by Abdullah et al. [92] that determined the different hydrolysis rates of cellulose and hemicellulose. Two steps of optimization of various conditions were considered. The first step was performed at less severity for hydrolyzing hemicellulose, whereas the second step was performed at high severity for cellulose depolymerization. Disadvantage of liquid hot water pretreatment is high energy consumption requirement for downstream process because of the involvement of large amount of water. However, the advantage of this process is that chemicals and catalysts are not required and no inhibitor is formed [60].
\nIn this pretreatment method, oxygen/air and water or hydrogen peroxide is used to treat biomass at high temperatures (>120°C) for half an hour at 0.5–2 MPa pressure [11, 93]. This pretreatment method is also used for the treatment of waste water and soil remediation. This method has proven to be very effective for pretreatment of lignin enriched biomass. Certain factors like reaction time, oxygen pressure, and temperature effect the efficiency of wet oxidation pretreatment process. Water acts like acid at high temperature, so it induces hydrolysis reaction as hydrogen ion concentration increases with increase in temperature which ultimately decreases the pH value. Pentose monomers are formed as a result of hemicellulose breakdown in wet oxidation pretreatment, and oxidation of lignin occurs, but cellulose remains least affected. There are certain reports on the addition of alkaline peroxide or sodium carbonate. The addition of these chemical agents help in bringing down temperature reaction and reduce the formation of inhibitory compounds. Efforts to improve the degradation of hemicellulose at high temperature lead to the formation of inhibitory compounds like furfural and furfuraldehydes. However, amount of the production of inhibitors in wet oxidation pretreatment is certainly less than that of liquid hot water pretreatment or steam explosion method. There is extremely less possibility of using this process at industrial scale because of two reasons. One is the combustible nature of oxygen, and the other is the high cost of hydrogen peroxide used in the process [94].
\nSPORL stands for sulfite pretreatment to overcome recalcitrance of lignocellulose, and this technique is used for pretreatment of lignocellulosic biomass [95]. SPORL is performed in two steps. The first step involves treatment of biomass with magnesium or calcium sulfite for the removal of lignin and hemicellulose fractions. The second step involves the reduction in size of pretreated biomass via mechanical disk miler. Effect of SPORL pretreatment was studied by Zhu et al. [22, 23] on spruce chips by employing conditions like temperature 180°C, half an hour time duration, 8–10% bisulfite, and 1.8–3.7% sulfuric acid. By employing these conditions, more than 90% substrate was converted to cellulose when cellulase of 14.6 FPU and 22.5 CBU β-glucosidase was used in hydrolysis. Low-yield inhibitors like hydroxymethyl furfural (HMF) (0.5%) and furfural (0.1%) were produced during this process. These percentages are far less as compared to acid-catalyzed steam pretreatment of spruce. In another study, SPORL-pretreated Popular NE222, beetle-killed lodgepole pine, and Douglas fir were purified. Low contents of sulfur and molecular mass were obtained with high phenolic derivative production [96].
\nSPORL pretreatment on switch grass with temperature ranging between 163 and 197°C, 3–37 min time duration, 0.8–4.2% sulfuric acid dose, and 0.6–7.4% sodium sulfite dose was performed by Zhang et al. [97]. The results with enhanced digestibility by the removal of hemicellulose due to sulfonation and decreased hydrophobicity of lignin were obtained. SPORL yielded 77.3% substrate as compared to 68.1% for dilute acid treatment and 66.6% through alkali pretreatment. When sodium sulfite, sodium hydroxide, and sodium sulfide were used in SPORL pretreatment of switch grass, an improved digestibility of switch grass was achieved. When SPORL treatment was applied with optimized conditions, 97% lignin and 93% hemicellulose were removed from water hyacinth, and 90% hemicellulose and 75% lignin were achieved for rice husk [98].
\nConventional methods for chemical and physical pretreatments require expensive reagents, equipment, and high energy. On the other hand, biological pretreatment requires live microorganisms for the treatment of lignocellulosic material, and this method is more environment friendly and consumes less energy. There are certain microorganism present in nature that exhibit cellulolytic and hemicellulolytic abilities. White-rot, soft-rot, and brown fungi are known for lignin and hemicellulose removal with a very little effect on cellulose. White rot is able to degrade lignin due to the presence of lignin degrading enzymes like peroxidases and laccases. Carbon and nitrogen sources are involved in the regulation of these degrading enzymes [41]. Cellulose is commonly attacked by brown rot, whereas white and soft rot target both lignin and cellulose contents of plant biomass. Commonly used white-rot fungi species are
Pretreatment of wheat straw was studied by Hatakka [100]. The results showed 13% conversion of wheat straw into sugars by
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
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\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{regionId:"6",sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. 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