Global ethanol production. Adapted from RFA [2008].
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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\r\n\tThe evaluation of the seismic hazard of a particular site represents the principal input data needed to develop the seismic code regulations and to perform structural building design worldwide. Being the actual trend of automatization of structural designs using various available software, it is imperative that structural engineers also study the estimation of earthquake ground motions and the associated risk of their designs, and seismologists envision in their research interests the structural analysis of buildings as well. Merging these technical fields would result in a new educational curriculum that would fulfill the actual research trends and demand practices. This book will address the recent advances, new perspectives, and applications of seismic hazard and risk evaluation based on the following topics: Tectonics, seismicity evaluation, ground motion prediction equations GMPEs, seismic hazard probabilistic methods, and site effects evaluation, including but not limited to inversion analysis on strong motion data and geophysical prospecting; development of structural fragility curves and seismic risk estimation.
",isbn:"978-1-83768-183-9",printIsbn:"978-1-83768-182-2",pdfIsbn:"978-1-83768-184-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"b2af07109b13b76e5af9583532ab5bee",bookSignature:"Dr. Walter Salazar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11999.jpg",keywords:"Seismicity Evaluation, Ground Motion Prediction, Historical Seismicity, Seismic Risk, Earthquake Catalogues, Recurrence Interval, Tectonics, Time-Independent, Time-Dependent, Response Spectra, Seismic Codes, Fragility Curves",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 26th 2022",dateEndSecondStepPublish:"July 29th 2022",dateEndThirdStepPublish:"September 27th 2022",dateEndFourthStepPublish:"December 16th 2022",dateEndFifthStepPublish:"February 14th 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"12 days",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A researcher in engineering seismology, practitioner, and teacher of structural engineering, formerly affiliated with the UWI Seismic Research Centre and EUCENTRE in Pavia-Italy to produce the first peer-review Seismic Hazard Maps for the Eastern Caribbean Islands. Dr. Salazar is a member of the Seismological Society of America (SSA) and Earthquake Engineering Research Institute (EERI).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"236461",title:"Dr.",name:"Walter",middleName:null,surname:"Salazar",slug:"walter-salazar",fullName:"Walter Salazar",profilePictureURL:"https://mts.intechopen.com/storage/users/236461/images/system/236461.jpg",biography:"Dr. Walter Salazar is a structural civil engineer who obtained a doctoral degree in Engineering Seismology from the Interdisciplinary Graduate School of Science and Engineering, Tokyo Institute of Technology, Japan, in 2004. Dr. Salazar has been active in site-effects and seismic hazard research, producing several peer-reviewed maps for El Salvador, Jamaica, and the Eastern Caribbean. He has published sixty articles in peer-reviewed journals, books, and international conferences. In 2011, he received a Distinguished Salvadoran National Award. He is a peer reviewer for several scientific journals. 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From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"17894",title:"Limitations and Challenges for Wheat-Based Bioethanol Production",doi:"10.5772/20258",slug:"limitations-and-challenges-for-wheat-based-bioethanol-production",body:'Bioethanol is currently the most widely used liquid biofuel in the world. Global ethanol production was ~19 billion L in 2000, and production has almost quadrupled over the past decade, with estimates for 2012 approaching 76 billion L [MRA, 2008]. In 2000, the total bioethanol produced in the U.S. represented 1.27% of the total gasoline pool by volume, and is expected to reach 7.5% of the gasoline pool by 2012 [EIA, 2007]. At present, bioethanol is produced exclusively via 1st generation technologies, utilizing sugar and starch-rich feedstocks, as no commercial size 2nd generation cellulosic ethanol facilities are presently in operation.
In countries like Canada, where wheat is locally available and abundant, the development of high yielding wheat-based bioenergy crops could contribute to reducing dependence on petroleum for transportation fuels and reduce green house gas (GHG) emissions. In order for wheat-based bioethanol to contribute maximally to the displacement of petroleum-based fuels, wheat varieties possessing characteristics optimized for end-use as bioethanol feedstocks are required. Wheat with characteristics tailored to the needs of the bioethanol industry would consist of high starch, low protein varieties, with the physicochemical parameters of the starch lending themselves to high conversion efficiencies under industrial conditions. However, no evaluative criteria of wheat starch quality, as it relates to maximized ethanol yield, is available. In this chapter, we review the rational for grain-based bioethanol production, the starch characteristics that would be optimal for a bioethanol feedstock, and propose selection criteria for development of dedicated, wheat-based, bioethanol feedstocks.
The largest ethanol producing industries, representing over 90% of the global 65.7 billion L produced in 2008 [CRFA, 2008], are located in Brazil and the United States of America (USA or US). Total production capacity in the U.S.A. is expected to reach about 90% of the 2015 goal of 56.2 billion L of corn ethanol production set in the 2007 Energy Independence and Security Act [Pryor, 2009]. In 2008, the USA produced 34 billion L (Table 1) of ethanol for use as fuel oxygenate. Most commercially made ethanol now comes from corn (~97.5% in USA) [Zhao et al., 2009] and the most commonly available blended gasoline contains 10% (E10) corn ethanol [Pryor, 2009; Tao & Aden, 2009]. Brazil produced approximately 24.5 billion L in 2008 but mandates 20-25% (E20-E25) blend ratios [Hahn, 2008]. According to Hahn [2008], the European Union (EU) has also set targets of 5.75% for blended gas, as has Argentina (at least 5%). China and India are also following this trend with nationa-wide fuel ethanol programs [Bai et al., 2008], as is Canada, which will need to produce 2 billion L of ethanol by 2010 to meet the 5% federal renewable fuel standard recently mandated [CRFA, 2009].
Ethanol has been mandated for incorporation into many countries transportation economies largely in the hopes of addressing rising concern over anthropogenic greenhouse gas emissions, of which 80% is claimed accountable to fossil fuel combustion [Quadrelli & Peterson, 2007]. The role of ethanol as a blended gasoline product, in ratios of 5 – 20% (v/v) ethanol, referred to as gasohol, can be used without major modifications to pre-existing automobile engines and burns cleaner, due to the higher octane rating, reducing harmful emissions [Agarwal, 2007]. Most researchers agree that a net decrease in GHG emissions of 13 – 18% is likely to be observed with the incorporation of ethanol as E10-20 into the fuel supply [Farrel, 2006; Kim & Dale, 2004, Dale, 2008]. Fuel security, volatility in oil pricing and the development of local, rural economies, have all been cited as additional impetus for many nation’s inclusion of biofuels into the energy policy discourse.
USA | 34.1 |
Brazil | 24.5 |
European Union | 2.8 |
China | 1.9 |
Canada | 0.9 |
Global ethanol production. Adapted from RFA [2008].
Most governments have helped their biofuel industries flourish with subsidies, suggesting these technologies are, at present, economically unviable. For example, subsidies per liter of ethanol total more than $6 billion (USD) per year for US corn ethanol [Pimentel et al., 2009; Koplow, 2006]. In Canada, between 2006 and 2008, total support to biofuels was between $860 million and $1.02 billion (CDN), averaging $300 million (CDN) per year [Laan et al., 2009]. However, at current energy prices, some agricultural feedstock have indeed already become competitive sources of energy, at least under certain production environments [Schmidhuber, 2006]. Sugarcane ethanol in Brazil is reported to offer higher energy return and greenhouse gas reductions per litre of ethanol than US-made corn ethanol [Rajagopal et al., 2007], and is suggested to be cost competitive with petroleum at US$25 per barrel (bbl) [Schmidhuber, 2006]. Regional variability in agricultural conditions, however, dictates the fuel crops that can feasibly be produced in an area. Sugarcane, for example, does not grow outside of tropical or sub-tropical climates. Starch-based bioethanol production, utilizing wheat and corn as feedstock, dominates the North American biofuels market, as these ubiquitous cereal grains are well suited to that environment.
Neither biofuels, nor any other petroleum alternative, are able to compete with fossil fuels if the price of oil is ≤ US$20/bbl, as it has been for most of the past three decades [Dale, 2008]. Dale [2008] claims that at ≥ US$50/bbl, many alternatives make economic sense, including some biofuels and particularly cellulosic ethanol. Without subsidies, at corn prices of around $3.25 per bushel, ethanol as a high-octane fuel is competitive with oil at about US$60/bbl [Dale, 2008]. Schmidhuber [2006] puts the parity price closer to US$58/bbl for maize-based ethanol in the US. In the past 4 years (April 2006 – April 2010) the average per barrel oil cost is cited as US$72.55 [EIA, 2010], and in that time per barrel oil price has been less than US$60 for only 6.5 months, where it averaged US$54.84 [EIA, 2010]. In fact, the growth in ethanol production, according to an Iowa State University study, has caused retail gasoline prices to be $0.29 to $0.40 per gallon lower than would otherwise have been the case [Du & Hayes, 2008]. Wheat-based ethanol production, which represents a large fraction of production in the EU and Canada, has less favorable economics than corn-based production. In the EU, grain-based ethanol production cost was reported in 2006/2007 as ~ $0.578/L [Tao & Aden, 2009], compared to ~ $0.396/L for corn purchased at $3.35 per bushel [Tao & Aden, 2009]. Although wheat represents a large fraction of production in the EU and Canada, only 1.6% of the total wheat harvest in Europe and 2.9% of the total wheat harvest in Canada was used for bioethanol production in 2007 [Harlander, 2008; Husky Energy, 2009].
Fossil fuels at present provide 85% of the commercial energy consumed worldwide [Lackner & Sachs, 2005] and 40% of the total energy consumption in the world is in the form of liquid fuels [Tan et al., 2008]. Global coal, oil, and natural gas reserves have been estimated to last for 218 years (coal), 41 years (oil), and 63 years (natural gas), under a business as usual scenario [Agarwal, 2007]. The world’s supply of low cost, “sweet” crude oil, however, is dwindling, with ‘peak oil’ having occurred or likely to occur before 2010 [Lackner & Sachs, 2005]. As the population swells towards 9 billion, it is estimated that oil demand will double in the rapidly developing economies of China and India, resulting in an estimated 52% increase in global oil demand by 2025 [IEA, 2005]. Projections for the 30-year period from 1990-2020 indicate that vehicle travel, and consequently fossil-fuel demand, will almost triple [Agarwal, 2007].
The development of an energy supply that is local, renewable and sustainable is highly desirable for nations with growing transportation fuel demands and who already import large fractions of their supply. For example, of the roughly 20 million barrels of crude oil the USA consumes daily [EIA, 2009a], almost 60% is imported [EIA, 2009b], making the US highly vulnerable to oil market fluctuations. China’s oil consumption has seen a purported 7.5% annual growth over the last several years, 7 times faster than the US [Luft, 2004]. In 2008, China consumed an estimated 7.8 million bbl/d and imported approximately 3.9 million bbl/d, roughly 50% of demand [EIA, 2010]. If the burgeoning economies of India and China place the predicted stress on oil availability and market price, this “would be the single most important aid and rationale for biofuels as a commercial reality” [Mousdale, 2008].
Despite the limitations of starch-based biofuels (see Section 4.0, below), the ease of ethanol’s adaptation to present oil infrastructure suggests that as gasoline prices increase and emission regulations become more stringent, ethanol is likely to assume a role of escalating significance in a market that no longer has access to cheap and abundant petroleum products. First generation bioethanol technologies offer an imperfect solution to the world’s long-term energy needs, whose utility must be viewed in context to locations that can feasibly support the diversion of food to energy crops. Adopting present processing technologies to utilize a feedstock, however, without the necessity of heavy cultivation and diversion of agricultural lands and foodstuffs, could represent a long-term solution to bioenergy generation and sustainable supply. Farrell [2006] claimed “large-scale use of ethanol for fuel will almost certainly require cellulosic (2nd generation) technology.”
Transportation biofuels such as cellulosic ethanol, if produced from low-cost biomass grown on agriculturally marginal land or from waste biomass, could provide much greater supplies and environmental benefits than food-based biofuels [Hill et al., 2006]. The US government, under the Energy Independence and Security Act of 2007, has mandated 16 billion gallons (~60 billion L) of “cellulosic ethanol” be included into the renewable fuel supply [Tao & Aden, 2009] by 2022. The cellulosic ethanol industry, however, remains nascent and has failed to emerge from the current demonstration phase to produce commercial-scale quantities. The US Environmental Protection Agency (EPA) recently acknowledged that, despite generous levels of taxpayer funding, cellulosic ethanol was not scaling up as quickly as had been hoped [Rapier, 2010] and previous targets outlined in 2007 have been significantly revised.
Starch-based ethanol production, although problematic, remains a mature technology capable of immediate contribution to the pressing global environmental and energy security needs. First-generation technologies are seen as an intermediate step to reduce GHG emissions and to diversify transport energy security [Antizar-Ladislao & Turrion-Gomez, 2008] whose production, however, is an undeniable aid in development of an ethanol infrastructure. Until cellulosic ethanol becomes a commercial reality, starch-based production will likely be of growing significance in many countries liquid fuel supply, especially for nations possessing large surplus quantities of grain, such as the EU, Canada and the USA.
Arguments in favor of starch-based ethanol production are countered by myriad of concerns related to land-use patterns and diversion of food supply, which generates significant uncertainty in the long-term utility of starch-based ethanol production. According to Rajagopal et al. [2007], production of biofuels takes land away from its two other primary uses – food production and environmental preservation. Some even argue that biofuels will cause dramatic changes in land-use patterns which could offset any CO2 savings derived from the utilization of biomass. Searchinger et al. [2008] contends that land-use changes will cause a net increase in GHG emissions with a doubling of GHG emissions over 30 years and increasing atmospheric CO2 concentrations for 167 years.
A number of sweeping condemnations of corn-based bioethanol production in the USA have been published in the past several years. The criticisms are centered around resource consumption, such as water, and agricultural practices: it has been estimated that a 50 million gallon per year ethanol factory consumes 500 gallons of water per minute, and that intensive corn production uses more nitrogen fertilizer [NAS, 2004], has significant phosphorus requirements [USDA, 2007], and uses more insecticides [Mclaughlin & Walsh, 1998] and herbicides [Patzek, 2004] than any other crop grown. Compounding these environmental issues is the reality of ethanol’s lower energy density. Ethanol delivers only two-thirds the energy that petroleum does and therefore more is required [Srinivasan, 2009].
Diverting food crops for use as substrate in biofuel production has caused unceasing controversy since the inception of the biofuels movement. In 2004, 13% of the US corn crop was diverted to produce ethanol [Patzek, 2004], in 2006 that number increased to 20%. In 2009/2010, 4.2 billion bushels of corn were used to produce ethanol, an increase from 3.6 billion bushels in 2008/2009 [USDA, 2009]. Overall, ethanol consumed 33% of the corn crop in 2009/2010, compared to 30% in 2008/2009. Some authorities have claimed that bioethanol production contributed to rising food prices, but these claims are controversial, and much uncertainty exists in the extent of the food price increases that may be attributed to bioethanol production [Sims, 2008]. For example, the use of corn for ethanol production was reported to have increased the prices of US beef, chicken, pork, eggs, breads, cereals, and milk by 10% to 20% [Brown, 2009]. However, in 2007 the UK, food prices increased even though no grain-based bioethanol was produced [Karl. 2010]
The switch to fuel crops, from other non-energy food crops, could cause additional food security issues. Projected corn ethanol production in 2016 would use 43% of the US corn land harvested for grain in 2004 [Searchinger et al., 2009]. According to Searchinger et al. [2009], U.S. agricultural exports will decline sharply causing a myriad of problems for importing nations, who will be forced to become increasingly self-reliant, likely appropriating previously unused land for domestic agricultural production. In June 2007, due to concern over rising food prices, China’s central government to ban the use of grain-based feedstocks for biofuel production and reoriented the country’s bioenergy plans toward perennial crops grown on marginal land [Weyerhaeuser et al., 2007]. In addition, Jacques Diouf, Director General of the UN Food and Agriculture Organization reported that using food grains to produce biofuels already is causing food shortages for the poor of the world [Diouf, 2007].
The most salient of arguments against 1st generation technologies are, however, (environmental and food diversion concerns aside), that grain-based bioethanol is “supply-limited” and cannot meet the expected US transportation fuel demand. Even if all current US soybean and corn production were dedicated to biofuels, only 12% of the gasoline demand and 6% of the diesel demand would be met [Srinivasan, 2009]. Globally seven crops (wheat, rice, corn, sorghum, sugarcane, cassava and sugar beet) account for 42% of cropland. If all land currently used to grow these crops were dedicated to biofuels, just over half of the global gasoline demand would be met.
As detailed above, feedstock sources for ethanol production vary around the world. Brazil, the largest ethanol producer, uses sugarcane as a primary feedstock source. Corn acts as the primary feedstock source in the United States. In Canada, corn is used as a feedstock for ethanol production in areas where grain corn can be produced. However, climatic conditions limit grain corn production in many areas. In western Canada, wheat is the most readily available, high quality feedstock. Therefore, the majority of proposals for expansion of ethanol production in western Canada include the construction of wheat-based ethanol plants.
Traditionally, Canadian wheat cultivars were developed to express high protein concentrations for functionality in the production of bread and pasta, extracting price premiums in the marketplace. High protein concentrations were accompanied, however, by low concentrations of starch, which make most small grain cereals less desirable for industrial ethanol production. Breeding efforts in the past 20 years have resulted in high-yielding wheat cultivars, such as those of the Canada Prairie Spring and the Canada Western Soft White Spring classes. Very high yielding triticale, hulless barley, and improved winter wheat cultivars have also been developed. All of these classes of small grains tend have protein concentrations between 10% and 14%, but their starch concentrations are mostly unknown [NRCan, 2003]. Starch concentrations are not generally determined, but reported as “total carbohydrates”, which are estimated as the difference between 100% and the sum of moisture, protein, crude fiber, fat and ash [Wolff, 1982]. In addition to starch and fermentable sugars, the ‘‘total carbohydrates’’ also contain water-soluble hemicellulose, β-glucans and pentosans, depending on the grain. Not all total carbohydrates are fermentable, and ethanol yields are overestimated when calculated from this parameter in cereal grains.
There is limited information regarding the potential ethanol yields of small grain cereals in western Canada. Wang et al. [1997] reported the spring triticale cultivar AC Copia yielded 362 to 367 L t-1 grain (14% moisture basis). Ethanol yields of 443 L t-1 of hulless barley (dry weight basis) have been reported [Thomas et al. 1995]. Thomas & Ingledew [1995] obtained 317 +/- 1.3 L t-1 on a dry weight basis from a hulled oat (cultivar unknown). Research in the USA reported that barley produced the greatest ethanol yield per hectare, slightly more than soft white spring wheat, while hard red and hard white spring classes produced the least [Lacerenza et al., 2008].
More recently, however, McLeod et al. [2010] evaluated the potential of small grains in western Canada to supply feedstock to the ethanol industry. Thirty-one lines and cultivars of Canadian small grains were evaluated: eleven cultivars comprising five classes spring wheat, six cultivars of barley (feed, malting, and hulless varieties), eight cultivars of spring triticale, and six cultivars of oat were grown at seven locations in western Canada and evaluated as feedstock for ethanol production. Starch concentrations and, for certain grains, β-glucan and pentosans were determined and used to estimate ethanol yields in L t-1 and L ha-1. On average, the ethanol yield in L t-1 was wheat > triticale > barley > oat.
Biologically, winter wheat has the highest yield potential of the
Starch is the predominant component of wheat grain, constituting 60-65% of the kernel. The functional properties of starch vary widely across botanical origin [Swinkels, 1985] and unique characteristics are desirable for different final product application [Franco et al., 2002]. Lacerenza et al. [2008] recently pointed out that the traditional selection criteria for wheat-breeding, based on milling and baking quality, is not consistent with maximal ethanol yield per hectare. The lack of breeding programs for varieties designed specifically for ethanol production, suggests Swanston et al. [2007], is due to a lack of appropriate selection procedures due to limited understanding of the factors contributing to alcohol yield.
Recent research into optimized bioethanol production has focused on the development of new and improved cereal and maize hybrids with higher starch contents to increase ethanol yields [Wu et al., 2006]. Grain preprocessing strategies are also being investigated and have the potential to ‘increase throughput rate and capacity of ethanol plants’ [Sosulski & Sosulski, 1994; Kindred et al., 2008] by decreasing non-starch carry-through. The outcome of present biofuel development is the inevitable processing of higher starch feed streams, achieved through adoption of new process technology or higher starch grains.
Starch content, although inarguably the most critical feature in determining ethanol conversion efficiency, is not necessarily the only influential parameter in understanding fermentation performance. Starch with high intrinsic resistance to enzymatic hydrolysis can yield a low sugar load to yeast, making it an erroneous selection as feedstock, especially when considering the industries move towards ever higher starch feed streams. Of particular interest to the bioethanol industry are the functional properties of starch that lend themselves to ease of amylolytic hydrolysis and high conversion efficiency of starch to fermentable sugars. The bioavailability of starch may differ among grain cultivars and may affect the conversion rate and final yield of ethanol [Moorthy, 2002]. A more thorough understanding of the influence starch structural and physicochemical properties have on the efficiency of gelatinization and liquefaction, the two most relevant industrial processes in the preparation of bioethanol feedstock, is therefore required.
Presently no evaluative criteria of grain starch quality, as it relates to maximized ethanol yield, are available to bioethanol producers. The following five parameters have been shown to influence the functional properties of starch and are used as evaluative criteria in this study: amylose/amylopectin content [Zhao et al., 2009; Wu et al., 2006, Wu et al., 2007; Lee et al., 2001]; starch granule morphology [Liu et al., 2007]; amylopectin fine structure [Zhang et al., 2008a; Ao et al., 2007; Sasaki et al., 2002; Zhang et al., 2008b]; thermal properties [Zhao et al., 2009; Wu et al., 2007]; pasting properties [Zhao et al., 2009].
Starch granules are composed of two types of alpha (α-)glucans, amylose (Figure 1) and amylopectin, which represent approximately 98-99% of the dry weight [Tester et al., 2008]. The ratio of the two polysaccharides varies according to the botanical origin of the starch, but within wheat varieties maintains ranges of 25-28% amylose and 72-75% amylopectin [Hung et al., 2006]. Starches with less than 5% amylose are found in “waxy” wheats, where as wheat varieties containing starches with greater than 35% amylose are considered “high-amylose” wheats [Wu
Wu et al. [2006] studied high-amylose starches and demonstrated that amylose content, more than protein or fiber content, had significant effect on ethanol fermentation efficiency. The study revealed that conversion efficiency decreased as amylose content increased. Starch in its native form is resistant to enzymatic digestion and must be gelatinized,
Amylose molecules composed of glucose monomers connected as in a) via α-(1,4)-glycosidic bonds or as in b) with infrequent branch chains via α-(1,6)-glycosidic bonds. Adapted from Saunders [2010].
changing it into an amorphous mass, before it becomes susceptible to glucosidic enzymes. Because of the existence of starch granules with high gelatinizing temperatures, and the formation of amylose-lipid complexes (AML) and reassociation of amylose molecules during gelatinization and enzymatic hydrolysis, there is always some starch that escapes hydrolysis by amylolytic enzymes [Boltz & Thompson, 1999]. As much as 2% of the starch in industrial dextrose production remained undigested as insoluble particles in the hydrolysate [Hebeda & Leach, 1974]. Amylose is likely to form amylose-lipid complexes in the caryopsis or during mashing that are resistant to enzymatic hydrolysis [Wu et al., 2007]. Wu et al. [2006] states that, in most instances, resistant starch content increases as the amylose content in starch increases. High amylose containing starches also inhibit fermentative ethanol production by yielding high viscosity mashes. Greater enzyme dosing, according to Wu et al. [2006], was not an effective strategy for increasing maltose and dextrin formation. It appears that high mash viscosity creates a bottleneck to enzymatic activity that can only be overcome with greater reaction time; greater reaction time, however, provides increased opportunity for deleterious retrogradation and amylose-lipid complexing, increasing the degree of insoluble sugars.
A reduction in amylose content has been positively correlated with enzymatic digestibility and represents the current accepted paradigm for the pattern of -amylolysis on native starches. Fermentation studies consistently report higher ethanol yields on waxy (high amylopectin) substrates than non-waxy counterparts. A high percentage of amylopectin seems to be more susceptible to α-amylase during fermentation, with higher gas production of waxy wheat flour as compared with the non-waxy wheat flour [Lee et al., 2001]. Wu et al. [2007] reported that waxy and hetero-waxy sorghum hybrids generally have higher conversion efficiencies than non-waxy hybrids. Zhao et al. [2009] studied the effects of waxy vs. non-waxy soft and hard wheats for fuel ethanol production and found results consistent with Lee at al. [2001] and Wu et al. [2007]. High ethanol conversion efficiencies of waxy-wheats were reported as compared to non-waxy wheats, (95.4 to 96.2% versus 92.6%, respectively) [Zhao et al., 2009]. Wu et al. [2006] observed that conversion efficiencies increased as the amylose content decreased, especially when the amylose content was >35%. Employing waxy wheat as feedstock for fuel ethanol production has been recommended [Lacerenza et al., 2008]. However, waxy-wheats have lower starch yields [Zhao et al. 2009] and no waxy wheat varieties have yet reached the commercial stage of development.
Present research suggests wheat starch has a trimodal distribution of granule sizes [41-43]. However, the existence of the smallest C-type granule remains somewhat putative with many authors reporting only the A and B-type granule populations [Ao & Jane, 2007; Morrison & Gadan, 1987; Peng et al., 1999]. A-type granules make up the bulk of starch (~75% by weight), but are fewer in number than the smaller sized B- and C-type granules (~25% by weight) [Ao & Jane, 2007]. A-type granules have been reported as 10-35 μm in average spherical diameter and account for less than 10% of the granules by number, small B and C-type particles therefore constitute over 90% of the granules by number [Lindeboom et al., 2004].
The large lenticular A-granules and the small, spherical B-granules have different physical, chemical and functional properties [Raeker et al., 2007; Morrison & Gadan, 1987; Dronzek et al., 1972; Kulp, 1973; Meredith, 1981; Soulaka & Morrison, 1985; Park et al., 2004]. The two types of granules (A- and B-) differ in their ratio of amylopectin to amylose [Morrison & Gadan, 1987; Soulaka & Morrison, 1985; Tester & Morrison, 1990], and have differing ratios of amylose to bound lipids [Raeker et al., 1998; Ao & Jane, 2007]. In cereal starches there are small quantities of naturally occurring lipids which are capable of forming complexes with amylose [Kwasniewska-Karolak et al., 2008]. The presence of amylose-lipid complexes negatively influence production of glucose syrups because it reduces water binding and swelling of starch granules, thus impairing the access of amylolytic enzymes [Matser & Steeneken, 1998]. Liu et al. [2007] studied the
Based on the findings of Liu et al. [2007], it appears that B-type granules may contain less resistant starch, due to lower concentrations of amylose, and may therefore yield higher conversion efficiency of starch to fermentable sugars during industrial feedstock preparation. The ratio of A- to B-type granules appears to vary significantly across cultivar type. However, a comparison of reported values across cultivars is challenging given genotype, environment, and method of analysis [Stoddard, 1999], which all appear to be influential in assessing the proportions of starch type in the granule. Various studies have reported B-granule distribution in wheat starch as ranging from 25-40% [Dengate & Meredith, 1984], others report the range as 13-34% [Soulaka & Morrison, 1985]. Recent studies, however, have yielded more detailed information regarding variation between wheat cultivars. For example, hard red winter (HRW) wheat was found to have 48.4% by volume classified as B-type (<10 μm diameter) [Bechtel et al., 1990]. In another study, B-granules occupied volumes in the range 28.5 – 49.1% (mean 39.9%) for HRW wheat, while hard red spring (HRS) wheat B-granules occupied volumes in the range 37.1 – 56.2% (mean 47.3%) [Park et al., 2009]. In a study by Raeker et al. [1998], thirty-four starch samples from soft wheat cultivars were investigated for differences in particle size distribution. It was found that contributions from the large granule population (>9.9 μm) to the total volume were 57.9 – 76.9%; B-type particles (<9.9 μm) therefore represent a range of 23.1 - 42.1% of total volume. However, Raeker et al. [1998] also reported a negative correlation between total starch and volume % of small granules (<10 μm) [Raeker et al., 1998]. In general, according to these findings, as starch content increases, a trait highly amenable to bioethanol production, the volumetric quantity of A-type granules present in the endosperm appears to increase, as small B and C-type granules decrease, a trait not necessarily desirable for end-use as ethanol feedstock.
The two key features of amylopectin fine structure are chain length distribution and branching pattern. According to Jenkins & Donald [1995], the currently accepted model for amylopectin structure involves short amylopectin chains forming double helices and associating into clusters. These clusters pack together to produce a structure of alternating crystalline (double helices) and amorphous lamellar composition (amylopectin branch points) [Jenkins & Donald,1995]. The branched chains of amylopectin, according to the cluster model of amylopectin proposed by Hizukuri [1986], can be fractionated into B3, B2, B1 and A chains that are described as follows: A-chains, DP 6-12; B1-chains, DP 13-24; B2-chains, DP 25-36; and B3-chains, DP >37. A and B1 chains dominate the distribution, forming double helices, with the longer B2 and B3 chains traversing two, three and four clusters (Figure 2) [Hizukuri,1986].
The dominance of certain fractions of side chain length dictates the type of crystallinity displayed during X-ray diffraction studies, referred to as A-type, B-type and C-type [Jenkins & Donald,1995]. Most cereal starches possess A-type crystallinity and have higher weights and number percents of short A chains [Chung et al., 2008]. Amylose is thought to exist mainly in the non-crystalline state [Hizukuri et al., 1996], but the exact location of amylose within the granule interior and the extent of its interaction with amylopectin is unclear [Gupta et al., 2009]. It is likely that a large portion is found within the amorphous (lamellae), with only small amounts associated with the semi-crystalline (lamellae) [Jenkins & Donald, 1995].
During starch gelatinization, starch granular or supramolecular structure is disrupted, resulting in the pattern of enzymatic hydrolysis being predominantly related to the inherent molecular structure of amylopectin [Zhang et al., 2008a]. The relationship between the molecular structure of starch (amylopectin fine structure) and its digestion rate after starch gelatinization is not well understood [Zhang et al., 2008b]. Little variation in the branching pattern of amylopectin has been reported in normal wheat starches. Hanashiro et al. [1996] reported the following distribution of amylopectin side chains after debranching: DP 6-12, 27%; DP 13-24, 49%; DP 25-36, 14%; and DP >37, 10%. These findings were
Structure of amylopectin depicted as ‘cluster model’ proposed by
supported in a study of 126 starch samples selected from the
Several studies have reported the effects of increasing branch density of amylopectin on decreased digestion rate of gelatinized starches through partial shortening of amylopectin exterior chains [Zhang et al., 2008a; Zhang et al., 2008b; Ao et al., 2007]. Ao et al. [2007] reported that starch products exhibiting high branch densities, with shorter average chain lengths, showed reductions in rapidly digested starch of up to 30% and concomitant increases in slowly digested starch of up to 20%. Zhang et al. [2008b] found that amylopectin of maize starch with high proportions of short chain fraction (SF, DP < 13) to long chain fraction (LF, DP > 13) showed increased quantities of slowly digested starch. The inherent molecular structure of amylopectin with a higher density of branches and shorter chains (high SF/LF ratio) is not favorable for rapid enzyme digestion [Zhang et al., 2008a]. In general, the findings of Ao et al. [2007] andZhang et al. [2008a] suggest longer branch chain lengths of amylopectin may be ideal for a rapidly digestible starch. In fact, waxy starches (>95% amylopectin), indicated as having favorable ethanol conversion performance, tend to have lower proportions of DP 6-12 side chains and higher proportions of DP >35 compared with non-waxy starches [Sasaki et al., 2002]. Future work is needed, however, to quantify the average amylopectin chain length optimal for rapid enzymatic digestion during liquefaction.
Gelatinization precedes liquefaction in the fermentation process and describes the physical break down of granular starch into solubilized, amorphous polymers readily hydrolyzed by -amylase and amyloglucosidase (AMG), the two enzymes responsible for the conversion of starch to sugar. This irreversible loss of native structure occurs when sufficient energy is applied to break intermolecular hydrogen bonds in the crystalline areas [Rooney & Pflugfelder, 1986]. Two endothermic peaks are seen when thermal properties are determined using differential scanning calorimetry (DSC) (Figure 3). The first peak represents the melting of amylopectin and the second peak corresponds to the melting of amylose-lipid complexes [Hung et al., 2006]. Gelatinization temperatures and enthalpies associated with gelatinization endotherms vary between starches. In a study by Gupta et al. [2009] native wheat and corn starch, measured at 70% moisture content, were reported to have onset temperatures (To) of 60.19 °C and 70.12 °C, respectively, peak temperatures (Tp) of 64.06 °C and 73.85 °C, respectively, and conclusion temperatures (Tc) of 68.42 °C and 78.20 °C, respectively.
Starch transition temperatures and gelatinization enthalpies by DSC may be related to characteristics of the starch granule, such as the amount of double helical domains (amylopectin) and single helical structures (amylose-lipid complexes) that unravel and melt during heating of aqueous starch dispersion. Van Hung et al. [2007] reported that waxy wheat starch with a predominant amylopectin content requires higher energy for gelatinization caused by its higher crystallinity as compared to non-waxy and high-amylose wheat starches. The presence of amylose, conversely, lowers the melting (gelatinization) temperature by decreasing crystallinity [Gupta et al., 2009].
Limited research has been performed to elucidate the relationship between gelatinization temperature and industrial fermentation efficiency. From an energy standpoint, low gelatinization temperature starch may be favorable as feedstock to produce fermentation-based products due to lower temperatures required to efficiently process the grain. Low gelatinization temperatures, however, are associated with high amylose content starch [Hung et al., 2006; Noda et al., 2002], previously demonstrated to be unfavorable to maximizing ethanol yield. Zhao et al. [2009] found waxy wheat starch to have complete disruption/dissolution of the granule at 70-80 °C, compared to non-waxy cultivars which showed evidence of intact granular structure under hot-stage microscopic visualization for temperatures as high as 90 °C. Wu et al. [2006] also reports that waxy starches easily gelatinize and have concomitantly high conversion efficiency. In regards to bioethanol production, the most salient thermal property is likely the point of complete
Thermal properties of starch. Endotherm of A) wheat and B) maize starch, showing the first and second endothermic peaks, related to amylopectin gelatinization and amylose-lipid dissolution, respectively. Adapted from
disruption/dissolution, as pointed out by Zhao et al. [2009], and not necessarily traditional transition temperature ranges, as is generally reported. Amylopectin content appears to be the most influential feature dictating total granular disruption and is perhaps, in this regard, the best predictive metric for ethanol conversion.
The relationship between amylopectin fine structure and the thermal properties of starch has been well established [Franco et al., 2002]. Starch that consists of amylopectin with a high proportion of long branch-chains purportedly displays higher gelatinization temperatures and enthalpy changes [Franco et al., 2002; Jane et al., 1999]. Several studies have reported the manipulation of branch chain length to modify thermal properties of starch. Amylopectin with increased quantities of longer branch chains produce more ordered double-helical crystallites, which require higher temperatures to uncoil and dissociate [Franco et al., 2002; Song & Jane, 2000; Huang et al., 2007]. Conversely, higher contents of extremely short chains within the amylopectin, DP 6 and 7, appear to lower To, Tp,and ΔH (gelatinization enthalpy) [Noda et al., 2002]. In regards to bioethanol production, driving down the gelatinization temperature by manipulating amylopectin branch chain length may lead to a substrate with lower energy requirements to achieve high conversion efficiency. However, the impact of amylopectin branch chain length on numerous other physicochemical properties [Franco et al., 2002; Noda et al., 2002], as well as enzymatic digestion rate [Zhang
Pasting viscosity profiles are analyzed using a Rapid Visco Analyzer (RVA). A typical profile is presented in Figure 4. The RVA curve describes pasting, a phenomenon following gelatinization, involving granular swelling, exudation of amylose and amylopectin, and total disruption of the starch granule. Pasting temperature is the point when the temperature rises above the gelatinization temperature, inducing starch granule swelling and resulting in increased viscosity. The peak viscosity indicates the maximum viscosity reached during the heating and holding cycle and is indicative of the water holding capacity of starch [Gupta et al., 2009], and peak temperature occurs at peak viscosity. The breakdown viscosity is normally regarded as a measure of the disintegration of the starch granules as they are heated [Agu et al., 2006] due to the rupture of granules and the release of soluble amylose. The degree of RVA breakdown is related to the solubility of the starch, and the more soluble the starch, the more it will thin on shearing [Hoseney, 1998]. As the mixture is cooled, re-association between starch molecules, especially amylose, results in the formation of a gel and the subsequent increase in viscosity. Total setback involves retrogradation, or re-ordering, of the starch molecule.
A typical RVA pasting profile showing the commonly measured parameters. Adapted from Saunders [2010].
Pasting properties of starch are affected by amylose and lipid contents and by branch chain-length distribution of amylopectin [Gupta et al., 2009]. Starches with larger amylose, lipid and phospholipid content have higher pasting temperatures, lower peak viscosity and shear-thinning (breakdown viscosity), and higher setback viscosity [Jane et al., 1999; Zeng et al., 1997]. Waxy wheat flour, conversely, has been shown to have significantly lower peak and pasting temperature, higher peak viscosity and lower setback viscosity than non-waxy or normal wheat flour [Gupta et al., 2009; Zeng et al., 1997; Abdel-Aal et al., 2002]. Waxy starch swells rapidly and swollen granules degrade at lower temperature, indicating that waxy starch rapidly develops viscosity but cannot maintain the stability of paste viscosity [Gupta et al., 2009]. Zhao et al. [2009] examined waxy starch granules using hot-stage microscopy and demonstrated that these starches rupture more extensively, even without mechanical shearing, and disperse more readily than non-waxy counterparts. Waxy wheat starch has been described as having lower final viscosity [Zeng et al., 1997; Abdel-Aal et al., 2002; Graybosch, 1998], an indication that it has less ability to retrograde and form strong gels.
Pasting properties, like thermal properties, are affected by the branch chain length distribution of amylopectin [Jane et al., 1999]. According to Franco et al. [2002], amylopectin with longer branch chains display larger peak viscosity and lower pasting temperatures than shorter chain counterparts. Jane et al. [1999] also reported that long chains with DP > 50 accelerated retrogradation of amylopectin, whereas the short chains (DP 6-9) retarded it. It is plausible that very long chains of amylopectin mimic amylose to form helical complexes with lipids and intertwine with other branch chains to hold the integrity of starch granules during heating and shearing [Gupta et al., 2009].
Wu et al. [2006, 2007] has described ideal feedstock for ethanol production as having rapid liquefaction characteristics and low viscosity during liquefaction. A high viscosity in the mash may impair the accessibility of starch to the enzyme and, thus, delay the liquefaction process [Wu et al., 2007]. The ideal pasting properties, as depicted by RVA analysis, of a starch destined for use as bioethanol substrate include high solubility, demonstrated by a low viscosity after breakdown, and limited ability to retrograde upon cooling, demonstrated by a low final viscosity. Modified RVA analysis was performed by Zhao et al. [2009] to assess the viscosity of waxy versus non-waxy wheat during gelatinization and liquefaction. In this case, conventional RVA analysis was modified to include dosing with -amylase, providing a metric for the balance between gelatinization and liquefaction. Zhao et al. [2009] states that “for waxy wheat cultivars, gelatinized starch granules were more susceptible to breakdown under liquefaction conditions; thus, starch molecules were more extensively exposed and more accessible to heat-stable -amylase, so lower peak viscosities were obtained. Due to the low peak viscosity for waxy wheat during liquefaction, the dry-grind industry could thus increase the solids content in the mash, lower -amylase dosages, or decrease energy requirements for stirring systems when waxy wheat is used as a feedstock.”
The inherent pasting characteristics of starches, such as peak viscosity, are not distinctly observed in modern fuel ethanol production processes because of the addition of α-amylase to the cooking/liquefaction step, to aid pasting and reduce viscosity. Hence, the pasting properties of any particular starch may not have as much influence on cooking/liquefaction as one might anticipate, although accessibility of starch molecules to -amylase would be a factor. The key is to have as much of the starch as possible (100%) converted to maltose and glucose in the saccharification step, which tends to be combined with fermentation in most modern processes.
Ethanol yield, perhaps the most important fermentation performance criteria for the fuel ethanol industry, has been shown to be a starch related property of wheat [Zhao et al., 2009; Lacerenza et al., 2008; Kindred et al., 2008]. Obviously a cultivar with higher starch content in its grain is desirable because it will provide more ethanol per ton of grain and produce smaller amounts of DDGS, resulting in less residual material left over and a greater energy saving during DDGS drying [Zhao et al., 2009]. Elite genotypes for ethanol production have been described as having rapid liquefaction characteristics, low viscosity during liquefaction, high fermentation speed and high fermentation efficiencies [Wu et al., 2007].
Starch properties conferring high conversion efficiencies to fermentable sugars, based on the available literature, are indicated in Table 2. Of particular note is the relationship of amylopectin to the majority of indicated parameters, and the marked benefit to each, in regards to bioethanol application, of an increase in amylopectin and concomitant decrease in amylose content. The encompassing recommendation of the present review is the selection of wheat with the highest amylopectin content achievable, theoretically delivering starch optimized for both rapid and complete degradation by industrial enzymes.
Amylose/Amylose Content | "/> 75% amylopectin | Wu Zhao |
Particle Size Distribution | High ratio of B-type granule | Liu |
Amylopectin Fine Structure | Increased long chain to short chain fraction | Ao |
Thermal Properties | Total disruption/dissolution of starch granule | Wu |
Pasting Properties | Low break-down, final & liquefaction viscosity | Zhao |
Ideal Physicochemical Parameters of Starch Recommended for Use as Bioethanol Feedstock.
Identification of genetic factors within wheat cultivars contributing to these parameters is a topic that has received, to date, little attention. Wheat cultivars producing ‘feed class’ grain with high starch content, and thus relatively low protein content, have been highlighted as the preferred ideotype for ethanol production [Sosulski & Sosulski, 1994; Kindred et al., 2008]. High starch, low protein content and high yield are reported as the most critical features of high ethanol producing wheat varieties. However, critical to starch conversion efficiency to fermentable sugars is the solubility of starch during gelatinization and the availability of solubilized material to liquefying enzymes. Therefore, a salient feature in the generation of varieties tailored to the needs of the bioethanol industry includes physicochemical parameters of starch lending themselves to high conversion efficiency under the conditions of liquefaction. High conversion efficiencies of starch to fermentable sugars will result in the greatest quantity of ethanol produced per unit of raw substrate when displayed in grains that exhibit both high yield and high starch content.
Considering the probable economic parity of starch-based ethanol with petroleum, it is still unlikely that starch-based ethanol production has the potential to singularly address long-term, global transportation fuel demand. However, despite the great potential of cellulosic technologies to offset petroleum consumption in the future, cellulosic bioethanol production is not yet competitive with either sugar-cane or starch-based bioethanol production, and it is likely that starch-based bioethanol will continue to be a major source of fuel ethanol. As nations move toward increasing incorporation of bioethanol into their transportation fuel supplies, it is likely that starch-based technologies will play a growing role, at least in the near future, in fulfilling that demand. In countries where wheat is a major agricultural crop, wheat-based bioethanol would benefit from the development of high starch, low protein varieties of wheat with characteristics that are ideally suited for bioethanol production (high amylopectin and low protein content). This would ensure access to stable supply, increase ethanol yields, and thus increase the economic viability of wheat-based bioethanol production.
Biofuels are of growing interest to many governments around the world as there is growing need to develop an energy supply that is local, renewable and independent of a financially volatile and potentially unreliable oil market.
Cellulose-based (2nd generation) conversion technologies, although possessing tremendous potential to displace the demand for petroleum-derived transportation fuels, remains a nascent industry.
Starch-based (1st generation) conversion technologies, although contentious in regards to diversion of food crops and land use patterns, are based on a mature industry capable of immediate contribution to pressing global, environmental and energy security needs.
Recent developments in 1st generation technologies suggest that starch feedstocks are being processed increasingly with no clear understanding of the role starch structure plays on conversion efficiency to ethanol.
Starch characteristics lending themselves to ease of amylolytic hydrolysis and high conversion efficiencies of starch to fermentable sugars would be desirable as bioethanol feedstock.
Properties of starch that appear to influence susceptibility to amylolytic attack include: amylose to amylopectin ratio, particle size distribution, amylopectin fine structure, gelatinization and pasting properties.
High amylopectin content appears to be the most meaningful predictive metric in assessing high conversion efficiency of starch to fermentable sugar.
Starch with a high proportion of the B-type granule may contain starch that is less resistant to enzymatic hydrolysis.
Amylopectin side-chain length fractions appear to vary little between wheat cultivars included in this review, making amylopectin fine structure an inappropriate metric for starch assessed as potential bioethanol feedstock.
Gelatinization temperatures indicating a high quantity of amylopectin, i.e. exhibiting high pasting temperatures (Tp), are likely well suited to bioethanol application as they degrade more completely than high amylose counterparts.
Pasting properties indicative of high amylopectin content suggest high solubility and low viscosity under the conditions of liquefaction.
Cereal grain cultivars previously identified as preferred bioethanol feedstock include high starch and low protein content, but should also include, based on the findings of this review, high amylopectin content starch.
Canine transmissible venereal tumor (CTVT) is the oldest known contagious cancer in dogs in the world. The first mention of this cancer occurred in the nineteenth century. It is also known as canine infectious sarcoma, canine venereal granuloma, canine transmissible lymphosarcoma, canine round cell sarcoma, and canine Sticker’s sarcoma [1, 2]. CTVT has an etiology like that of other contagious cancers, such as devil facial tumor disease (DFTD), which originates from an abnormal cell line with an unlimited proliferative capacity [3, 4]. CTVT can be transplanted via viable cancer cells that naturally allograft between CTVT-infected dogs and uninfected hosts via physical transfer [4].
Previous studies suggest that CTVT cell lineage might be up to 10,000 years old [5]. The clonal origin of CTVT was proven through the analysis of microsatellite polymorphisms, mitochondria DNA (mtDNA), dog leukocyte antigen (DLA) typing, and genome sequencing. It has been suggested by phylogenetic analysis that CTVT emerged between 4000 and 8500 years ago in Asia [6, 7, 8, 9]. CTVT is now a common disease worldwide that has been reported on all inhabited continents. However, CTVT has a higher prevalence in tropical and subtropical regions and is uncommon in North America and Northern and Central Europe, although occasional cases have been reported in imported dogs [5, 10]. An interesting feature of this cancer is that it is usually curable via several protocols. However, metastasis, chemotherapeutic resistance, and death are still reported in CTVT cases in endemic areas, especially in immunosuppressed dogs [1, 11].
The carcinogenesis of CTVT remains unclear. This cancer may be caused by many sources, but all CTVT cells share the same genetic rearrangement [12]. Specifically, the long interspersed nuclear element-1 (LINE-1) in CTVT cells shows a difference from normal dog cells or host cells [12]. This evidence demonstrates that CTVT clonal evolution grows along the host, and the genetic instability and numerous mutations of CTVT cells give them contagious abilities [6, 8].
Remarkably, CTVT cells are usually transplanted through physical transmission from one dog to another during sexual intercourse. The violent exertions associated with intercourse in both genders are prone to causing genital mucosal damage, which enables the transmission of viable CTVT cells to susceptible hosts. The tumor starts to grow as solitary or multiple nodules at the glans penis or bulbus glandis area in the male dog and on the mucosa wall of the vagina or vulva in the female dog [13]. Cancer cells can affect the mucosa of the external genital organs, skin, and other sites on the body [14, 15, 16, 17, 18, 19]. Transplantation occurs individually across the major histocompatibility complex (MHC) between the cancer cells of the CTVT-infected dog and the damaged mucosa of the susceptible dog [1, 2]. CTVT can evade the host’s immunological detection, allowing its worldwide spread as a naturally occurring allograft cancer in dogs because its cells lose the expression of MHC class I and II molecules. The growth of a CTVT mass in the external genital area usually appears within 2–6 months after mating [13]. CTVT was the first tumor to be experimentally transplanted by Novinsky in 1876. The CTVT mass cannot be grown with cells that have been treated with glycerin or cell-free filtrates or cells that have been frozen or heated [13]. Even though this contagious cancer has been described as having only dogs as its specific host, CTVT can be heterotransplanted experimentally by inoculation between dogs (
The CTVT mass frequently manifests in the external genitalia of the dog after transmission through coitus. However, other parts of the body can be affected by this cancer. CTVT can be classified into two types according to its anatomical location: lesions typically located on the external genital area of both male and female dogs are called genital TVT (GTVT), while those found in extragenital areas (including subcutaneous, the mucosa of eyes, and in nasal and oral cavities) are called extragenital TVT (ETVT). The GTVT mass at the external genital area is observed as a cauliflower-like mass feature that is friable tissue with hemorrhage or presents with serosanguinous and hemorrhagic discharge and possible secondary bacterial infection [1, 2, 11, 14, 15, 16, 17, 18]. ETVT may be related to social behaviors among dogs because of the means of species communication—for example, licking, sniffing, fighting during the breeding season, and routine socialization. As such, the ETVT type is found more frequently in males than in females due to natural behaviors (Figure 1) [13].
Gross lesion of genital TVT (1A, 1B) and extragenital TVT (1C, 1D).
CTVT has remarkable cytogenetic features. There is an aberration in the number of chromosomes of CTVT. Normally, the normal number of chromosomes in the somatic cells of dogs is 78, 76 acrocentric chromosomes, and couple of metacentric sex chromosomes [7, 21]. Conversely, the number of chromosomes in the CTVT cells varies from about 58–59, with 13–17 metacentric and 42 acrocentric chromosomes and no sex chromosome [1, 7, 13]. These cytogenetic features are consistent and unique and are found in both GTVT and ETVT. This chromosome pattern also appears in CTVT cell cultures and in experimental transplantation [24].
CTVT is one of the round cell tumors, according to its cytomorphologic features. GTVT cases are easier to diagnose according to the location (genital areas) and shape (oozing cauliflower-like mass) of their gross lesions [25]. The CTVT mass can be 0.5 to 10 cm in diameter. Histologic examination of the predictable growth pattern of CTVT reveals numerous round-to-ovoid-shaped cancer cells arranged in a diffuse pattern with an abundance of mitotic figures and few TILs, supported by thin trabeculae of fibrovascular tissue [23]. There are some neutrophils, lymphocytes, macrophages, and plasma cells. The CTVT cell passaging tumor showed no change in the histology of the tumor during the experimental passage [13]. However, the atypical anatomical lesions in ETVT cases are more ambiguous to diagnose based on their location and gross lesion because their features depend on their affecting sites. For example, they perform like a button mass with ulceration when they are located subcutaneously or on the skin. On the other hand, they display irregular shapes in the conjunctiva and oral and nasal cavities. The ETVT tumor must be differentiated from other types, including mast cell tumor, histiocytic tumor, lymphoma, amelanotic melanoma, and poorly differentiated carcinoma, which depends on the anatomical site of the lesion and the characteristics of the histologic examination [25].
Cytologic diagnosis is of great value for easy and rapid on-site diagnosis [26]. As mentioned before, CTVT is one of the round cell tumors, so the main populations of CTVT cells are round-to-ovoid-shaped cells that may originate from the histiocytic system. To improve cytologic knowledge, researchers found that there are three types of cytomorphologic classification of CTVT, which are categorized by the cell morphology of the majority population: (1) lymphocytic type, characterized by more than 60% of round cells, with fine granular cytoplasm, central nuclei, and few intracytoplasmic vacuoles; (2) plasmacytic type, characterized by containing more than 60% of cells with broad cytoplasm, eccentric nuclei, and large amount of vacuoles; and (3) mixed type, presenting both lymphocytoid and plasmacytoid cells, neither of which exceeds 59% [26, 27]. Recently, a study with computerized cytomorphometric analysis of round cells revealed that CTVT had the largest cellular and nuclear size which followed by the histiocytic tumor cell, mast cell tumor, and lymphoma cell. CTVT cell from GTVT case had the largest cellular and nuclear size followed by CTVT cell from ETVT case, histiocytic tumor cell, mast cell tumor cell, and lymphoma cell. According to the CTVT cytomorphologic type, the mixed type had the largest cellular and nuclear size followed by the plasmacytic and lymphocytic type. The researchers have revealed that the plasmacytic type is the most common cytomorphologic type [27, 28]. The plasmacytic type [26, 27, 28, 29, 30] and the mixed type [26] are related to malignant behaviors and chemotherapeutic drug resistance. The lymphocytic type shows aggressive behavior less than other types [26]. So, cytomorphologic classification can provide a prognostic for treatment in each CTVT case (Figure 2).
Cytomorphology of CTVT cells presents the lymphocytic cell type (arrow) and plasmacytic cell type (star); H&E (40X).
Most canine round cell tumors have been immunocharacterized using several tumor markers—for example, cluster of differentiation 3 (CD3), CD79, paired box-5 protein (PAX-5), and protein-tyrosine kinase (c-kit and CD117). Diagnosis and classification using the immunophenotype are more accurate than routine histopathologic examination. However, the cell origin of CTVT is unclear. CTVT has been previously described as lymphosarcoma, a round cell sarcoma, a histiocytoma, and a tumor of neuroectodermal or reticuloendothelial origin [23]. Immunohistochemistry studies revealed that CTVT cells are negative for keratins, α-smooth muscle actin, desmin, CD3, immunoglobulins G and M, γ-light chains, and κ-light chains. These panels ruled out epithelial, smooth muscle, and T- and B-lymphocytes. CTVT cells are positive for vimentin, ACM1, lysozyme, and alpha-antitrypsin (AAT). Lysozyme and alpha-antitrypsin are not expressed by other mesenchymal cells. Moreover, ACM1 is a canine-specific antibody recognized in canine mononuclear phagocyte stem cells. This panel immunophenotypic expression suggests that CTVT has a histiocytic origin because this set of antigens is not expressed by other mesenchymal round cells [23].
CTVT has unique molecular characteristics. CTVT has the rearrangement of the c-
CTVT cells respond to many forms of therapy. Historically, CTVT has been treated with surgical excision therapy and followed by several chemotherapeutic cocktails or a combination of chemotherapeutic protocols or radiotherapy. Surgery is chosen for a localized CTVT mass, but it is not recommended in generalized or metastatic cases. Electrosurgery and cryosurgery are optional surgical methods because the tumor is easily transplanted to surgical wounds when using the conventional surgical method. The rate of recurrence after conventional surgery was between 12 and 68% [13]. Surgical methods have a higher recurrence rate than chemotherapy. Radiotherapy was chosen as the therapy for CTVT cases with complete regression within 1–3 treatments of a dose of 10 Gy or 1000 rad. Although radiotherapy is a successful treatment, this method requires sedation for dogs, specialized technicians, and expensive equipment [13].
The original combining protocol was composed of vincristine, cyclophosphamide, and methotrexate. Also, there have been attempted combination protocols, such as cyclophosphamide and prednisolone, vinblastine with cyclophosphamide, vinblastine with methotrexate, and vincristine with ivermectin [13]. After clinical evaluation and development of chemotherapy for CTVT treatment, the use of vincristine, vinblastine, and doxorubicin, as single agents were attempted. The duration of vincristine for complete remission is around 4–6 weeks of intravenous administration at a weekly dose of 0.025 mg/kg bodyweight [11, 32]. CTVT cases are treated using vinblastine intravenously in a dose of 0.1 mg/kg bodyweight on four to six weekly treatments [13]. Moreover, complete remission was also reported within three weeks in the doxorubicin treatment when given intravenously at a weekly dose of 30 mg/m2 surface area [19, 32]. Vincristine has been reported as the most effective, safe, and convenient agent for GTVT and ETVT cases. The better response to vincristine treatment may be due to less myelosuppression compared to doxorubicin and no immunosuppression by methotrexate. However, weight loss, mild leukopenia, and gastrointestinal toxicity, such as anorexia, nausea, and vomiting, are common adverse effects of vincristine treatment in less than 10% of cases. An additional complication of vincristine treatment is the extravasation of the drug during administration causing necrotic ulcer lesions of the affected skin [19].
Recently, the combination of vincristine (VCR) and L-asparaginase (LAP) protocol or VCR-LAP protocol has demonstrated an effective treatment result and shorter treatment time than VCR alone. The VCR-LAP combination protocol is given in alternating weekly doses of 5000 IU/m2 of LAP subcutaneously and 0.025 mg/kg of VCR intravenously. The duration of combination protocols is 2–5 weeks, with no evidence of VCR-resistant cases. The short period of treatment provides fewer opportunities for chemotherapeutic drug resistance. Moreover, the combined protocol costs less on average than mono-chemotherapy [11]. A comparative treatment study via a murine model of vascular targeted photodynamic therapy was performed as the new strategy for chemotherapeutic-resistant cases [33]. Moreover, VCR-resistant status is still increasing, not only in ETVT cases but also in GTVT cases [11, 32, 34]. When only partial remission was noted in seven and eight weeks, a 30 mg/m2 dose of doxorubicin was administered as mono-chemotherapy every three weeks for a total of five treatments [19]. The duration of doxorubicin treatment was around three applications or two months. In addition, four treatments of vincristine 0.025 mg/kg bodyweight with LAP 10,000 IU/m2 every two weeks were also used in resistance cases that showed complete regression [34].
The best thing for veterinarians to keep in mind is that this contagious cancer can be treated with chemotherapy and achieve complete regression. Also, the mono-chemotherapeutic drug VCR can cure this cancer and is recommended as the chemotherapeutic drug of choice for CTVT treatment. Recovery rates are high in more than 90% of cases and have been documented by using VCR at a 0.025 mg/kg body weight dosage over two to eight weeks. The mixed and plasmacytic cytomorphologic types show malignant behavior related to vincristine-resistant and recurrent cases [26]. However, the lymphocytic type has been shown to be less malignant than other types. The larger cell size or the increase in the cellular and nuclear size of tumor cells may demonstrate the survival ability of cells and the progression of tumor grading [35, 36]. Also, the lymphocytic type was found in GTVT cases and was not related to metastasis behavior [26]. According to the anatomical lesion, this can infer that GTVT has a lower malignant behavior than ETVT [11, 26]. In VCR treatment cases, the lymphocytic type had the shortest time to complete regression. The prognosis of treatment with VCR is influenced by the stage of growth, the cytomorphologic type, the size of the tumor, the anatomical site of the mass, and the climate [13, 26, 32]. Recurrence of CTVT was rare because of the effectiveness of chemotherapy. However, some recurrent cases were reported six months after complete remission. So, long-term monitoring after cessation of treatment should be more than six months (Figure 3) [11, 32].
The lesion at the penis before (3A) and after complete remission (3B).
The CTVT mass grows mostly on male and female external genital areas due to live cell transmission during coitus. The highest risk periods are the estrus and breeding periods. No breed predisposition has been documented, but mixed breed dogs were reported in 41% [19] to 100% [11] of cases. Dogs of any age are susceptible to CTVT. CTVT is most commonly found in intact dogs between two and five years of age. The mean ages of the affected dogs were 3.9–4.5 [13]. GTVT is never found in virgin dogs. Also, the tumor is more common in females than males due to one infected male often interacting with many females, both in breeding kennels and endemic areas [13]. Older dogs showed more ETVT evidence than GTVT, which is more common in intact young adult dogs. Poor body condition scores and immune status might be cofactors in aging dogs with ETVT [11].
Researchers have been interested in and attended the roles of host immunity response in the P-phase and R-phase of CTVT. In experimental transplantation, CTVT can evade immune surveillance and show rapid growth for 12 weeks. The spontaneous regression of both natural and experimental transplantation suggests that the host immune response plays a major role in CTVT. Moreover, immunosuppressed dogs and puppies develop more aggressive CTVT masses that lack TILs, and these masses are rarely eliminated and hardly show complete remission [2]. The differences between the P-phase and the R-phase are the presence and number of TILs. Thus, the complete regression and complete response to treatment may depend on the appropriate immune response of host cells, which is related to the immune status of the CTVT-susceptible dogs. CTVT cells evade immune detection during the transmission period and growth phase by secretion of transforming growth factor β (TGF-β). TGF-β is a multifunctional protein that controls cellular differentiation and proliferation, which acts as a suppression activity of class I and II MHC expression and natural killer (NK) cell activity. Conversely, TGF-β is countered by interleukin-6 (IL-6), which is produced by TILs [20, 37].
CTVT cells show the tumor-associated antigen and shed into the circulation during the P-phase, and this CTVT tumor-associated antigen could no longer be detected after surgical removal of the CTVT mass [13]. This CTVT tumor-associated antigen was detected using antibodies against the antigen during the P, S, and R phases [38]. The amount of this antigen released in the host circulation increased alongside the increase in tumor volume. There is evidence that humoral immunity plays a role in the P-phase. This antigen may be responsible for blocking the host’s immune response in the P-phase. The infiltration, the presence of B cells, and the upregulated expression of the groups of genes related to B cells were mentioned in the signature of acute allograft rejection [13]. Thus, humoral immunity also plays an important role in inhibiting and preventing CTVT tumor development and acute CTVT allograft rejection in many case studies. This emphasizes that CTVT itself has been reported to be antigenic and can evoke tumor rejection in the host’s immunity.
In naturally occurring CTVT, spontaneous regression was also observed, albeit less frequently than in the experimental transplanted CTVT [32]. The dogs that have recovered are immune to reinoculation [1]. Passive immune transfer of post-regression sera to CTVT-bearing dogs has been shown to inhibit and prevent tumor development. Moreover, the growth of CTVT is inhibited in puppies born to dams that are immunized for CTVT before or during pregnancy [2]. CTVT cells have more membrane-bound antibodies in the S and R phases than in the P-phase. The absence of antibodies in puppies with metastasis suggest the importance of humoral immunity in progression. The metastatic rate is low—less than 20% in GTVT cases [9, 19]. Metastatic cases have been reported in subcutaneous tissues, skin, lymph nodes, eyes, tonsils, liver, spleen, oral mucosa, nasal mucosa, brain, and bone marrow [15, 21, 32, 39]. Although metastasis is not common in CTVT cases, it can be a serious situation and the cause of death.
Recently, researchers have found that inflammation and epithelial cell proliferation may characterize the early response to VCR treatment in the early stage [40]. CTVT in the R-phase after treatment showed that the expression of many groups of genes occurred at the same time, with pathological changes of not only macroscopic features but also microscopic ones. The group of inflammation genes was the most upregulated in the S-phase, and the immunologic groups of genes involved in T-cell, NK-cell, and B-cell function were upregulated in the R-phase. In this late R-phase, there was a loss of CTVT cells and cell migration but an increase in fibrosis that is related to new tissue formation or the healing stage [23, 40]. This finding revealed the process that started with the inflammatory response, epithelial and keratinocyte proliferation and followed by the host T-, NK- and B-cell infiltration, and finished with the cell cycle arrest. In addition, Bcell-related genes, albeit less prominent in quality and expression levels than T- and NK-cell panels, were also progressively upregulated [40]. This is related to previous studies that showed that the infiltration and presence of B-cell was the signature of acute allograft rejection [41].
The interferon (IFN) for neoplasia treatment is initially based on the nonspecific activating host immune response. Normally, type I IFN has the ability to inhibit tumor cell growth and induce tumor cell apoptosis in the in vitro studies [42]. During the R-phase of CTVT growth, the IL-6 and interferon-γ or Type II IFN from the host plays a special role in enhancing MHC molecule expression on antigen-presenting cells, activating NK-cell activities, and modulating B lymphocyte responses [20, 37, 43]. An in vitro study of interferon type I for CTVT treatment found that interferon ω showed the effect of inhibiting CTVT cell viability in a dose-dependent manner [44]. CTVT case treatment by immunotherapy is of interest to many researchers. Recently, the combination protocol of intratumoral interferon-α2a with VCR shortened the treatment duration when compared with VCR alone [45]. Thus, combining a low-dose chemotherapeutic drug and immunotherapy may be advantageous for CTVT patients because of the initial trigger of inflammation by chemotherapy, synergizes with the activation of the host immune response by interferon. The VCR triggers host interferon signal expression, which induce NK-cell and lymphocyte infiltration. The addition of interferon may enhance the innate and adaptive responses of mononuclear cells and might affect CTVT viability and proliferation. The change in environment and the increase in inflammatory production by local host cells after treatment with VCR may trigger and recruit immune cells. The strong response induced by VCR causes the release of damage-associated molecular patterns from stressed or apoptotic cells as an innate immune response of the host, which induces direct cognition of foreign DLA molecules and ultimately leads CTVT to regression. In addition, this evidence suggests that combining the low dose of chemotherapy with immune checkpoint therapy may help the host immune response against CTVT by inducing the inflammation for tumor regression (Figure 4) [40].
Histopathologic features of CTVT tissue at week 0 or before treatment with vincristine (4A) and two weeks after treatment (4B).
Stray dogs and poor policy control are the predisposed causes of CTVT transmission [19]. Thus, the control of CTVT transmission is difficult because free-roaming dogs and their intact status represent a reservoir [9, 13]. Prevention is related to government policy, maintenance of spay and neuter campaigns, and animal feeding practices in each country [9]. CTVT cases are found more often in rural areas than in urban areas because of a lack of adequate veterinary services [13]. Currently, CTVT is estimated to be found at a prevalence of 1–10% or more in dogs in many countries on all inhabited continents. CTVT is endemic in at least 90 countries worldwide. The highest prevalence of CTVT was recorded in Belize, where the prevalence was 10–20%. However, prevalence is decreasing in North America and central and northern Europe [9]. New owners and breeders should conduct a careful physical examination before adoption or breeding, especially in imported dogs. Dog licensing laws, spay and neuter encouragement campaigns, and controlling stray or free-ranging dogs should be emphasized to reduce physical contact between infected and uninfected dogs. Also, long-term monitoring of 6–12 months after cessation of treatment should be performed and this practice should be encouraged among veterinarians in endemic areas.
CTVT is the only naturally occurring contagious cancer in dogs. This oldest canine cancer spreads through the physical transfer of whole viable cancer cells between hosts. The specific host, transmission, gross lesion, microscopic features, growth pattern, immunologic relative host response, molecular characteristics, and responsiveness to treatment of CTVT are of interest to researchers and practitioners. Genital CTVT cases are visually noticeable and are easier to diagnose and treat than extragenital CTVT cases. The conventional single chemotherapeutic agent VCR has delivered curable treatment in most CTVT cases during 4–6 chemotherapeutic cycles. However, vincristine-resistant cases have been increasing in number. This decade has revealed more treatment options, such as VCR–LAP combination protocol. By contrasting the anatomical features of the two types of cases and the VCR-resistant cases, this paper highlights that the GTVT type is more noticeable and curable than the ETVT type.
The authors gratefully acknowledge generous funding from the Center of Excellence for Companion Animal Cancer, Department of Veterinary Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand. C. Setthawongsin was supported by the Kasetsart University Research and Development Institute (KURDI) and the Department of Veterinary Technology, Faculty of Veterinary Technology, Kasetsart University, Bangkok, Thailand.
The authors declare no conflict of interest.
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While the first two modes focus almost exclusively on government actors, CCM goes beyond them by involving private sectors and civil society. CCM is a more robust form of crisis governance since it combines knowledge and resources from multiple actors, which is a key to managing the more complex nature of modern crises. This chapter uses the case of Indonesia in dealing with the COVID-19 pandemic to show the dynamics of crisis governance. Indonesia moved from a centralized mode of crisis governance toward a more decentralized one. Simultaneously, there were several collaborative initiatives involving multiple stakeholders to deal with the crisis, such as in the case of SONJO. The case illustrates that while CCM provides a more effective response, it has some limitations as it has a smaller scale, may create internal conflict, lacks sustainability, and has a nonbinding character. The experience of Indonesia lends the lesson that for CCM to be robust crisis governance, and there needs to be a clear arrangement to boost its scale, manage internal conflict, improve sustainability, and induce a more permanent and binding framework.",book:{id:"11439",title:"Crisis Management - Principles, Roles and Application",coverURL:"https://cdn.intechopen.com/books/images_new/11439.jpg"},signatures:"Gabriel Lele"},{id:"82858",title:"Corporate Social Responsibility a Case of the Provision of Recreational Facilities",slug:"corporate-social-responsibility-a-case-of-the-provision-of-recreational-facilities",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105608",abstract:"Corporate social responsibility (CSR) connotes Government agencies and private enterprises services for effective change and in this regards the recreational provision. The inadequate provision of the recreational services thwarted recreation, resulting to unsuitable funding of recreational facilities and unsuccessful synergy between government and the private enterprises embarking on CSR. This paper examines the roles of government and the private enterprises in the services of CSR with the view to enhance their performances in the provision of recreational facilities. The paper applied the qualitative method using atlas ti.8 for the data analysis. The findings reveal inadequate facilities provision for recreation resulting from lack of funding, lacklustre attitude and poor synergy of the stakeholders. The paper recommends that government should be positive in implementing policies that promote recreational activities and improving the efforts of the private enterprises for CSR. With the effectiveness and efficiency of the provision of recreation facilities, CSR will be acknowledged as a case of Greater Jos. Plateau State, Nigeria.",book:{id:"11602",title:"Corporate Social Responsibility",coverURL:"https://cdn.intechopen.com/books/images_new/11602.jpg"},signatures:"Peter Musa Wash, Shida Irwana Omar, Badaruddin Mohamed and Mohd Ismail Isa"},{id:"82786",title:"Discussion of Purchasing Virtual Digital Nature and Tourism",slug:"discussion-of-purchasing-virtual-digital-nature-and-tourism",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.105869",abstract:"This chapter discusses the potential and prospects of consumers purchasing virtual digital nature and smart tourism. During the lockdown period, people experienced a trend toward increased subjective well-being as a result of their familiarity with the digital nature. In order to academically validate these experiences, this study examines how interaction with nature in the digital environment stimulates new consumer behavior in post-pandemic life. The study will apply structural equation modeling (SEM) to 300 data collected through a questionnaire to develop the discussion, with a particular focus on the mediating effects of digital forest bathing. The results show that digital forest bath ing has a mediating effect in stimulating people’s environmentally oriented behavior, and that the more active they are in digital space and interact with others, the more consumers enjoy interacting with nature in cyberspace and, in turn, the more willing they are to commune with digital nature through smart tourism. This can be expected to provide an effective reference for marketing strategies that contribute to the promotion of smart tourism in the age of symbiosis with COVID.",book:{id:"11581",title:"A New Era of Consumer Behavior - Beyond the Pandemic",coverURL:"https://cdn.intechopen.com/books/images_new/11581.jpg"},signatures:"Hiroko Oe and Yasuyuki Yamaoka"},{id:"82777",title:"Sustainability and Social Investment: Community Microhydropower Systems in the Dominican Republic",slug:"sustainability-and-social-investment-community-microhydropower-systems-in-the-dominican-republic",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.105995",abstract:"Sustainability remains an underestimated concept when assessing the impact of philanthropic and social investments in communities due to the difficult task of conciliating human development, economy, and environmental protection. Currently, financial cost-effectiveness is one of the main criteria for decision-making. However, under a social investing and climate justice framework, monetary valuation of impacts is never enough to assess the complexity of livelihoods. A multi-stakeholder approach, based on common objectives and synergy among entities, is key for sustainability and social investments. Public institutions, private sector, international cooperation, and local civil society organizations work together in the development of initiatives that promote integral development. In the Dominican Republic and Haiti, community microhydropower systems have proved to be an effective model of social investment, climate justice, and sustainability. The response to a social need, such as access to electricity, has turned into a means for promoting a different approach, based on community empowerment. This article contains the experience of the successes and challenges of more than 50 community microhydropower systems, managed by local groups, which are working and demonstrating the meaning of sustainability and the positive nonmonetary impacts of social investing, opening future opportunities to expand the present 5% of private investment.",book:{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg"},signatures:"Michela Izzo, Alberto Sánchez and Rafael Fonseca"},{id:"81403",title:"Do the Collaboration Dimensions Pay in Manufacturing Reverse Supply Chain? An Empirical Approach",slug:"do-the-collaboration-dimensions-pay-in-manufacturing-reverse-supply-chain-an-empirical-approach",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.103068",abstract:"The purpose of this paper is to examine empirically the enablers and practices of collaboration in relation to reverse supply chain. The research method used in this research was a quantitative method using a survey approach to empirically test if the following collaboration enables and practices are applicable. The statistical approach was AMOS 26. The findings revealed that, the relationship building and management for implementing collaboration was ranked highest, resource investment and development in reverse supply chain was ranked the next. Furthermore, quick response on returned goods and information sharing with suppliers on the returned products were highest ranked. The research was limited because the study was based in the Gauteng region, which means that a generalised statement cannot be made of the finding, as well there is a need for the study to be industry specific such as electronics, online retailers. The practical implications of the findings are that the enablers and practices are needed for reverse supply practices to achieve its aims. There is lack of research in the reverse collaboration space, this has paper has fulfilled the following gap.",book:{id:"11253",title:"Sustainable Rural Development",coverURL:"https://cdn.intechopen.com/books/images_new/11253.jpg"},signatures:"Ifije Ohiomah, Clinton Aigbavboa and Nita Sukdeo"},{id:"82387",title:"Kept Promises? The Evolution of the EU Financial Contribution to Climate Change",slug:"kept-promises-the-evolution-of-the-eu-financial-contribution-to-climate-change",totalDownloads:11,totalDimensionsCites:0,doi:"10.5772/intechopen.105541",abstract:"The chapter provides an overview of the public climate finance implemented under the UNFCCC by the EU as a whole and its Member States—in the chapter called EUplus—later taken over by SDG 13.a, for the period 2011–2018 (the latest year available). Through the analysis of the UNFCCC Biennial Reports, it is possible not only to highlight the amount allocated to the challenge against climate change, but also to break it down into its two meanings: mitigation and adaptation, as well as to identify the type of channel through which this support has been implemented. In this context, particular attention will be given to the two contribution channels: bilateral and multilateral, highlighting the type of support in different cases. The chapter shows an increase in contributions, especially since 2015, and how support has been increasingly shifted toward adaptation. This could mean that there is an awareness in a delay in achieving the stabilization of GHG emissions in the atmosphere.",book:{id:"11476",title:"Globalization and Sustainability - Recent Advances, New Perspectives and Emerging Issues",coverURL:"https://cdn.intechopen.com/books/images_new/11476.jpg"},signatures:"Cecilia Camporeale, Roberto Del Ciello and Mario Jorizzo"}],onlineFirstChaptersTotal:71},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. 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He previously worked as a post-doctoral fellow at the Ben-Gurion University of Negev, Israel; University of the Free State, South Africa; and Central University of Technology Bloemfontein, South Africa. He obtained his Ph.D. in Organic Chemistry from Nagaoka University of Technology, Japan. He has published more than seventy-four journal articles and attended several national and international conferences as speaker and chair. Dr. Kendrekar has received many international awards. He has several funded projects, namely, anti-malaria drug development, MRSA, and SARS-CoV-2 activity of curcumin and its formulations. He has filed four patents in collaboration with the University of Central Lancashire and Mayo Clinic Infectious Diseases. His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. Prof. Emeje was a national chairman of academic pharmacists in Nigeria and the 2021 winner of the May & Baker Nigeria Plc–sponsored prize for professional service in research and innovation.",institutionString:"National Institute for Pharmaceutical Research and Development",institution:{name:"National Institute for Pharmaceutical Research and Development",country:{name:"Nigeria"}}},{id:"436430",title:"Associate Prof.",name:"Mesut",middleName:null,surname:"Işık",slug:"mesut-isik",fullName:"Mesut Işık",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/436430/images/19686_n.jpg",biography:null,institutionString:null,institution:{name:"Bilecik University",country:{name:"Turkey"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. 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