Summary of key aspects of the four molecular subgroups of medulloblastoma.
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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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This book provides valuable information about the toxicity of several agrochemicals that can negatively influence the health of humans and ecosystems.',isbn:"978-1-83880-047-5",printIsbn:"978-1-83962-647-0",pdfIsbn:"978-1-83880-048-2",doi:"10.5772/intechopen.78909",price:119,priceEur:129,priceUsd:155,slug:"pesticides-use-and-misuse-and-their-impact-in-the-environment",numberOfPages:136,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"420a19fa07c8510eeb08decebed430cc",bookSignature:"Marcelo Larramendy and Sonia Soloneski",publishedDate:"July 17th 2019",coverURL:"https://cdn.intechopen.com/books/images_new/8533.jpg",numberOfDownloads:9193,numberOfWosCitations:4,numberOfCrossrefCitations:35,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:100,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:139,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 30th 2018",dateEndSecondStepPublish:"September 20th 2018",dateEndThirdStepPublish:"November 19th 2018",dateEndFourthStepPublish:"February 7th 2019",dateEndFifthStepPublish:"April 8th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"14764",title:"Dr.",name:"Marcelo L.",middleName:null,surname:"Larramendy",slug:"marcelo-l.-larramendy",fullName:"Marcelo L. Larramendy",profilePictureURL:"https://mts.intechopen.com/storage/users/14764/images/system/14764.jpg",biography:"Marcelo L. Larramendy, Ph.D., serves as Professor of Molecular Cell Biology at the School of Natural Sciences and Museum (National University of La Plata, Argentina). Appointed Senior Researcher of the National Scientific and Technological Research Council of Argentina. Former Member of the Executive Committee of the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis. Author of more than 450 contributions, including scientific publications, research communications and conferences worldwide. Recipient of several national and international awards. Prof. Larramendy is a regular Lecturer at the international A. Hollaender Courses organized by the IAEMS and former guest scientist at NIH (USA) and the University of Helsinki, (Finland). He is an expert in Genetic Toxicology and is, or has been, referee for more than 20 international scientific journals. Member of the International Panel of Experts at the International Agency for Research on Cancer (IARC, WHO, Lyon, France) in 2015 for the evaluation of DDT, 2,4-D and Lindane. Presently, Prof. Dr. Larramendy is Head of the Laboratory of Molecular Cytogenetics and Genotoxicology at the UNLP.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"20",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"14863",title:"Dr.",name:"Sonia",middleName:null,surname:"Soloneski",slug:"sonia-soloneski",fullName:"Sonia Soloneski",profilePictureURL:"https://mts.intechopen.com/storage/users/14863/images/system/14863.jpg",biography:"Sonia Soloneski has a Ph.D. in Natural Sciences and is Assistant Professor of Molecular Cell Biology at the School of Natural Sciences and Museum of La Plata, National University of La Plata, Argentina. She is a member of the National Scientific and Technological Research Council (CONICET) of Argentina in the Genetic Toxicology field, the Latin American Association of Environmental Mutagenesis, Teratogenesis and Carcinogenesis (ALAMCTA), the Argentinean Society of Toxicology (ATA), the Argentinean Society of Biology (SAB) and the Society of Environmental Toxicology and Chemistry (SETAC). She has authored more than 380 contributions in the field, including scientific publications in peer-reviewed journals and research communications. She has served as a review member for more than 30 scientific international journals. She has been a plenary speaker in scientific conferences and a member of scientific committees. She is a specialist in issues related to Genetic Toxicology, Mutagenesis, and Ecotoxicology.",institutionString:"National University of La Plata",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"306",title:"Pesticides",slug:"pesticides"}],chapters:[{id:"65801",title:"The Morphophysiological, Histological, and Biochemical Response of Some Nontarget Organisms to the Stress Induced by the Pesticides in the Environment",doi:"10.5772/intechopen.84332",slug:"the-morphophysiological-histological-and-biochemical-response-of-some-nontarget-organisms-to-the-str",totalDownloads:1103,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Ferns, amphibians, and fish are groups of nontarget organisms affected by many types of pesticides that end up in the environment. This chapter aims to approach the following themes: the influence of different pesticides on the spore germination process and on the differentiation of their gametophyte; aspects regarding the impact of some pesticides on breathing in fish (physiology and histopathology at the branchial level), as well as a series of effects at the hematological and biochemical levels; and changes of some hematological, biochemical, and structural parameters in amphibians. Species that are not directly targeted by the action of the pesticide in the environment, ferns can be used in their gametophyte stage, young or mature sporophyte in different biotests to evaluate the risk associated with these substances. The biochemical, hemathological, and histopathological changes recorded in both fish and amphibians can be considered biomarkers of pesticide pollution.",signatures:"Liliana Cristina Soare, Alina Păunescu and Ponepal Cristina Maria",downloadPdfUrl:"/chapter/pdf-download/65801",previewPdfUrl:"/chapter/pdf-preview/65801",authors:[{id:"276263",title:"Associate Prof.",name:"Liliana Cristina",surname:"Soare",slug:"liliana-cristina-soare",fullName:"Liliana Cristina Soare"},{id:"289058",title:"Dr.",name:"Cristina Maria",surname:"Ponepal",slug:"cristina-maria-ponepal",fullName:"Cristina Maria Ponepal"},{id:"289059",title:"Dr.",name:"Alina",surname:"Păunescu",slug:"alina-paunescu",fullName:"Alina Păunescu"}],corrections:null},{id:"66132",title:"Metabolic Impairments Caused by Pesticides in Mammals and Their Interactions with Other Pollutants",doi:"10.5772/intechopen.84966",slug:"metabolic-impairments-caused-by-pesticides-in-mammals-and-their-interactions-with-other-pollutants",totalDownloads:927,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The biological systems are exposed to a complex environment in which the contaminants can interact in a synergistic/antagonistic fashion and for this reason, the study of “chemical cocktails” is of great interest to fully understand the final biological effect. To evaluate the final biological response of a pollutant, it is essential to have an adequate analytical methodology that allows the correct monitoring of environmental systems in order to establish their quality, and, when appropriate, the application of corrective measures. Undoubtedly, massive methods “the omics” are among the most efficient current tools. To this end, transcriptomics, proteomics, metabolomics and chemical speciation can provide very useful information, mainly when they are combined. However, the combination of proteomics with metabolomics has some drawbacks as the temporal space is different (i.e. metabolomics gives information about what happens right now, but it can be related with numerous post-translational modifications happened previously). In this sense, it seems that the combination of genomics with metabolomics is easier. Thus, when metabolomics data are interpreted in combination with genomic, transcriptomic and proteomic results, in the so-called systems biology approach, a holistic knowledge of the organism/process under investigation can be achieved.",signatures:"Gema Rodríguez-Moro, Ana Arias-Borrego, Sara Ramírez-Acosta, Francisco Navarro-Roldán, Nieves Abril-Díaz, Rut Fernández-Torre, Miguel Angel Bello-López, José Luis Gómez-Ariza and Tamara García-Barrera",downloadPdfUrl:"/chapter/pdf-download/66132",previewPdfUrl:"/chapter/pdf-preview/66132",authors:[{id:"34564",title:"Prof.",name:"José Luis",surname:"Gómez-Ariza",slug:"jose-luis-gomez-ariza",fullName:"José Luis Gómez-Ariza"},{id:"39335",title:"Dr.",name:"Miguel-Angel",surname:"Bello-Lopez",slug:"miguel-angel-bello-lopez",fullName:"Miguel-Angel Bello-Lopez"},{id:"39336",title:"Dr.",name:"Rut",surname:"Fernández-Torres",slug:"rut-fernandez-torres",fullName:"Rut Fernández-Torres"},{id:"39337",title:"Dr.",name:"Nieves",surname:"Abril",slug:"nieves-abril",fullName:"Nieves Abril"},{id:"274852",title:"Prof.",name:"Tamara",surname:"García-Barrera",slug:"tamara-garcia-barrera",fullName:"Tamara García-Barrera"},{id:"303409",title:"Dr.",name:"Gema",surname:"Rodríguez-Moro",slug:"gema-rodriguez-moro",fullName:"Gema Rodríguez-Moro"},{id:"303410",title:"Dr.",name:"Ana",surname:"Arias-Borrego",slug:"ana-arias-borrego",fullName:"Ana Arias-Borrego"},{id:"303411",title:"Dr.",name:"Sara",surname:"Ramírez-Acosta",slug:"sara-ramirez-acosta",fullName:"Sara Ramírez-Acosta"},{id:"303412",title:"Dr.",name:"Francisco",surname:"Navarro-Roldán",slug:"francisco-navarro-roldan",fullName:"Francisco Navarro-Roldán"}],corrections:null},{id:"64602",title:"Environmental Risk of Groundwater Pollution by Pesticide Leaching through the Soil Profile",doi:"10.5772/intechopen.82418",slug:"environmental-risk-of-groundwater-pollution-by-pesticide-leaching-through-the-soil-profile",totalDownloads:3058,totalCrossrefCites:22,totalDimensionsCites:66,hasAltmetrics:1,abstract:"Adsorption, degradation, and movement are the key processes conditioning the behavior and fate of pesticides in the soil. Six processes that can move pesticides are leaching, diffusion, volatilization, erosion and run-off, assimilation by microorganisms, and plant uptake. Leaching is the vertical downward displacement of pesticides through the soil profile and the unsaturated zone, and finally to groundwater, which is vulnerable to pollution. Pesticides are frequently leached through the soil by the effect of rain or irrigation water. Pesticide leaching is highest for weakly sorbing and/or persistent compounds, climates with high precipitation and low temperatures, and soils with low organic matter and sandy texture. On the contrary, for pesticides with a low persistence that disappear quickly, the risk of groundwater pollution considerably decreases. Different and varied factors such as physical-chemical properties of the pesticide, a permeability of the soil, texture and organic matter content of the soil, volatilization, crop-root uptake, and method and dose of pesticide application are responsible for the leaching rate of the pesticides. Soils that are high in clays and organic matter will slow the movement of water, attach easily to many pesticides, and generally have a higher diversity and population of soil organisms that can metabolize the pesticides.",signatures:"Gabriel Pérez-Lucas, Nuria Vela, Abderrazak El Aatik and Simón Navarro",downloadPdfUrl:"/chapter/pdf-download/64602",previewPdfUrl:"/chapter/pdf-preview/64602",authors:[{id:"202983",title:"Dr.",name:"Simón",surname:"Navarro",slug:"simon-navarro",fullName:"Simón Navarro"},{id:"202988",title:"Dr.",name:"Nuria",surname:"Vela",slug:"nuria-vela",fullName:"Nuria Vela"},{id:"206059",title:"Dr.",name:"Gabriel",surname:"Pérez-Lucas",slug:"gabriel-perez-lucas",fullName:"Gabriel Pérez-Lucas"},{id:"283154",title:"Mr.",name:"Abderrazak",surname:"El Aatik",slug:"abderrazak-el-aatik",fullName:"Abderrazak El Aatik"}],corrections:null},{id:"65766",title:"Pesticides, Anthropogenic Activities, and the Health of Our Environment Safety",doi:"10.5772/intechopen.84161",slug:"pesticides-anthropogenic-activities-and-the-health-of-our-environment-safety",totalDownloads:1454,totalCrossrefCites:7,totalDimensionsCites:16,hasAltmetrics:1,abstract:"Mankind depends on agricultural products for food consumption. Increasing population (more than 7 billion) requires significant growth in crop yield to meet essential demand. This aim was achieved through the use of pesticides to protect crops from diseases. Pesticides are toxic by design for organisms that can threaten food products. Their mode of action is by targeting systems or enzymes in the pests that may be similar to human system and therefore pose risks to human health and the environment as well. The WHO recommended classifying pesticides according to their toxicity and chemicals according to their chronic health and environmental hazards.",signatures:"Mona Saud AL-Ahmadi",downloadPdfUrl:"/chapter/pdf-download/65766",previewPdfUrl:"/chapter/pdf-preview/65766",authors:[{id:"276726",title:"Ph.D.",name:"Mona",surname:"AL-Ahmadi",slug:"mona-al-ahmadi",fullName:"Mona AL-Ahmadi"}],corrections:null},{id:"65752",title:"Uses and Misuses of Agricultural Pesticides in Africa: Neglected Public Health Threats for Workers and Population",doi:"10.5772/intechopen.84566",slug:"uses-and-misuses-of-agricultural-pesticides-in-africa-neglected-public-health-threats-for-workers-an",totalDownloads:1556,totalCrossrefCites:4,totalDimensionsCites:8,hasAltmetrics:1,abstract:"Pesticides are use in agriculture for their capacity to reduce pest and protect foods. Since their introduction in Africa by colonial masters, the use of these chemicals is constantly growing. Herbicides and insecticides are the two dominant categories. Although they are used in small quantities by farmers who own small exploitation, the frequency of their use, as well as overuses and misuses, constitutes serious factors of exposure and health risks. Farm workers are more vulnerable to occupational effects from pesticide inhalation and skin contacts. Failure to wear protective equipment and observe good agricultural practices explained health symptoms that are frequently experienced: eye and skin irritation, nausea, vomiting, and headache. Population is subject to chronic health effects due to repeated dietary intake of pesticides. Most consumed staple foods on the continent (cereals, vegetables, and fruits) have been found to be contaminated by one or multiple residues of pesticides. The level of residues is often higher than regulatory limits. Organization of surveillance programs to monitor concentration of pesticide residues remains inexistent in most countries, same for toxicovigilance systems to documented poisoning cases. Current data underline the need to carry out pesticide health risk assessment in order to appreciate the threats they pose for public health.",signatures:"Pouokam Guy Bertrand",downloadPdfUrl:"/chapter/pdf-download/65752",previewPdfUrl:"/chapter/pdf-preview/65752",authors:[{id:"276832",title:"Ph.D. Student",name:"Guy Bertrand",surname:"Pouokam",slug:"guy-bertrand-pouokam",fullName:"Guy Bertrand Pouokam"}],corrections:null},{id:"66189",title:"Pesticides, Anthropogenic Activities, History and the Health of Our Environment: Lessons from Africa",doi:"10.5772/intechopen.82600",slug:"pesticides-anthropogenic-activities-history-and-the-health-of-our-environment-lessons-from-africa",totalDownloads:1096,totalCrossrefCites:1,totalDimensionsCites:5,hasAltmetrics:0,abstract:"This chapter describes the historical events related to pesticide use. The description of events focuses on human activities that necessitated the use of chemical agents for pest control to protect crops, and animals including humans in African countries. The description covers the common pests in Africa and the need for pest control using pesticides. History of pesticide use in Africa and the ban of organochlorines are covered. Controversies under discussion in Africa and the current trend of pesticide use in Africa are part of the chapter as well as pesticide import and supply. Hazard and risk of exposure of biological organisms including humans to pesticides due to anthropogenic activities in Africa and pros and cons of pesticide use in Africa are covered.",signatures:"Wilbert Bunini Manyilizu",downloadPdfUrl:"/chapter/pdf-download/66189",previewPdfUrl:"/chapter/pdf-preview/66189",authors:[{id:"274792",title:"Dr.",name:"Bunini",surname:"Manyilizu",slug:"bunini-manyilizu",fullName:"Bunini Manyilizu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"4637",title:"Toxicity and Hazard of Agrochemicals",subtitle:null,isOpenForSubmission:!1,hash:"6aff74df1ea32df7f1e20e29c8363ff5",slug:"toxicity-and-hazard-of-agrochemicals",bookSignature:"Marcelo L. 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\r\n\tThe book Trichoderma aims to assist in the integrated management of plant diseases with applications in all cultivation systems (including vegetables, cereals, oilseeds and fruit trees). Parasitism, identification of species, ultrastructure and molecular aspects (uses of SSR and snips techniques) of the interaction of the biocontrol agent and the seeds, roots and the phyllosphere will also be discussed, taking into account all the modalities of use of this important and versatile microorganism. Aspects of its application involving products and their formulations for use by farmers, as well as management tactics involving other biocontrol agents such as bacteria, use of organic matter, vegetation cover and resistant or tolerant varieties for some pathosystem will also be addressed.
\r\n\r\n\tThe book will discuss integrated management of plant diseases and plant protection, with an emphasis on phytopathogenic fungi, biocontrol, plant genetics and resistance.
",isbn:"978-1-80355-355-9",printIsbn:"978-1-80355-354-2",pdfIsbn:"978-1-80355-356-6",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"adeba4522858a6406df7ad737a4f1956",bookSignature:"Dr. Fernando Cezar Cezar Juliatti",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11317.jpg",keywords:"Mechanisms of Trichoderma Species, Morphology, Identification, Molecular Techniques, Uses and Field Application, Bioprospecting, Systemic Acquired Resistance (SAR), Resistance, Fungicides, Integrated Pest Management (IPM), Biocontrol, Application Modes",numberOfDownloads:292,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 3rd 2021",dateEndSecondStepPublish:"October 1st 2021",dateEndThirdStepPublish:"November 30th 2021",dateEndFourthStepPublish:"February 18th 2022",dateEndFifthStepPublish:"April 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Juliatti is the Professor and Researcher at the Federal University of Uberlândia and President of the Brazilian Association of Agriculture Education. He is a Winner of the 2011 Top Ethanol Award and Winner of the Top Science Award in 2008 and 2013.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"146372",title:"Dr.",name:"Fernando",middleName:"Cezar",surname:"Cezar Juliatti",slug:"fernando-cezar-juliatti",fullName:"Fernando Cezar Juliatti",profilePictureURL:"https://mts.intechopen.com/storage/users/146372/images/system/146372.jpg",biography:"Dr Fernando Cezar Juliatti is a professor and researcher, born in Ribeirão Vermelho Minas Gerais state, Brazil. He obtained a degree in Agronomy from the School of Agriculture of Lavras/UFLA (1981), a master's degree in Agronomy (Phytopathology) from the Federal University of Viçosa/UFV (1985) and a PhD in Agronomy (Plant Breeding) from Federal University of Lavras/UFLA (1994). He was head of the Department of Agronomy at Federal University of Uberlândia (UFU) in 1995 and 1996 . From 1998 to 2000, he presided over the implementation of the Graduate Program in Agronomy at Federal University of Uberlândia (master's and doctorate). He was director of the Institute of Agricultural Sciences at Federal University of Uberlândia from 2001 to 2004. He was president of the Brazilian Society of Phytopathology in the period from 2003 till 2004. Dr Juliatti is a member of the Brazilian Societies of Phytopathology, Plant Breeding and Brazilian Horticulture in addition to the Paulista Group of Phytopathology. He is technical consultant in the areas of corn and soybeans/ phytopathological problems in the Brazilian savannah. \nHe and the Plant Improvement team at Federal University of Uberlândia developed strains of soybean, tomato and beans with multiple resistance to phytopathogens. Together with this team, he launched 05 protected soybean cultivars for the Brazilian savannah with multiple resistance to important soybean pathosystems, including partial resistance to Soybean Asian rust. \nHe chaired the organizing committee of the Brazilian Congress on Agroenergy and the First International Symposium on Biofuel. He coordinated the Chamber of Agronomy of CREA-MG (in 2008 and 2009) and the National Coordination of Agronomy of the CREA / CONFEA system (in 2009). He is a coordinator of the Latin American Committee on studies on Sclerotinia (Sclerotinia International Working Group). Dr Juliatti is a Financial Director of SMEA (Minas Gerais Society´ of the Agronomy Engineers) and current member of the Fiscal Council of the same entity. He is also President of ABEAS (Brazilian Association of Higher Agricultural Education - Triennium 2011-2013 and 2013-2016). He is Winner of the 2011 Top Ethanol Award in the area of technological innovation in industrial energy offered by UNICA and Winner in 2008 and 2013 of the Top Science Award offered by the company Basf. S.A.\nDr Juliatti is a permanent professor in the Graduate Programs in Agronomy (UFU, Brazil - Master and Doctorate) and Biofuels (UFU-UFVJM - Master and Doctorate). He was the Technical Director for four terms at the Association of Agricultural Engineers of Triângulo Mineiro and Alto Paranaíba, Minas Gerais, Brazil. He was President of the Triângulo Mineiro and Alto Paranaíba Association (AGROTAP), from 2017 to 2018 . In 2017 he was President of 50 Brazilian Congress of Phytopathology (Golden Jubilee) and 16 International Workshop on Sclerotinia and II Brazilian Workshop on Soybean Rust. Currently he is coordinator of the UFU Agronomy Course at the Campus Uberlândia. He published more 200 articles in important journals from Brazil and other countries, 11 books and 12 chapters in the field of Agronomy.",institutionString:"Federal University of Uberlândia",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"13",title:"Immunology and Microbiology",slug:"immunology-and-microbiology"}],chapters:[{id:"80375",title:"Trichoderma: A Biofertilizer and a Bio-Fungicide for Sustainable Crop Production",slug:"trichoderma-a-biofertilizer-and-a-bio-fungicide-for-sustainable-crop-production",totalDownloads:131,totalCrossrefCites:0,authors:[null]},{id:"81107",title:"Can Genus Trichoderma Manage Plant Diseases under Organic Agriculture?",slug:"can-genus-trichoderma-manage-plant-diseases-under-organic-agriculture",totalDownloads:85,totalCrossrefCites:0,authors:[null]},{id:"80357",title:"Trchoderma Spp.: Their Impact in Crops Diseases Management",slug:"trchoderma-spp-their-impact-in-crops-diseases-management",totalDownloads:77,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"418641",firstName:"Iva",lastName:"Ribic",middleName:null,title:"M.Sc.",imageUrl:"https://mts.intechopen.com/storage/users/418641/images/16830_n.png",email:"iva.r@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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However, it is found in infants and adults as well. Arising from embryonal cells in the cerebellum, medulloblastoma is a highly invasive cancer which unfortunately manifests initially with subtle clinical symptoms [2]. While conventional treatments are able to control the tumor in the majority of patients, debilitating side effects along with drug resistance remain significant concerns. For the clinician, one of the challenges to treating medulloblastoma is its complexity as it may be grouped either histologically or molecularly. Currently, there are four molecular subgroups of medulloblastoma, each of which contains specific genetic or cytological backgrounds which may impact prognosis [3].
\nMedulloblastoma is classified as a primitive neuroectodermal tumor, typically occurring in the cerebellar vermis which is located in the posterior fossa of the skull (Figure 1) [1]. This tumor accounts for 40% of those arising from the posterior fossa [4]. Medulloblastoma is the most common malignant central nervous system (CNS) tumor of childhood, comprising 15–30% of pediatric CNS tumors and 1–3% of adult CNS tumors [5]. Medulloblastomas can affect any age group, although the majority (85%) occurs in childhood, and of those half occur between the ages of 4–9 [6]. Tumors most often arise sporadically, although they may arise as part of inherited disorders such as Li-Fraumeni, Turcot, or Gorlin syndrome [7]. The cellular origins of medulloblastoma differ by the tumor subgroup (described below). For example, medulloblastomas of the sonic hedgehog (SHH) subgroup arise from granule neuron progenitors (GNPs) that reside in the outermost layer of the cerebellum [8]. Wnt-subgroup medulloblastomas, on the other hand, arise from lower rhombic lip precursors in the brainstem [9].
\nMedulloblastoma is a primitive neuroectodermal tumor commonly arising in the cerebellar vermis. The left image is a sagittal view of an MRI for a pediatric patient. The right image is a horizontal view of an MRI showing tumor growth towards the right cerebellar hemisphere, with displacement of the vermis. Copyright © 2014 from
Given that the cerebellum is located against the fourth ventricle, tumors arising from it result in mass effect and hydrocephalus. Consequently, patients initially diagnosed with medulloblastoma present most commonly with symptoms of elevated intracranial pressure—chronic progressive nausea, vomiting, and headache [10]. These symptoms can progress to altered mental status, sensorimotor symptoms, and cerebellar symptoms if left untreated [10]. Children and infants may present instead with nonspecific lethargy and weakness. Neurological signs, often subtle, may be present for 3 or more months before diagnosis [11].
\nMedulloblastoma metastasizes most commonly to the spinal cord. In an international meta-analysis of medulloblastoma, metastatic disease was identified in 103 of 432 patients (24%) on initial diagnosis [6], although the incidence was much lower in adults (2%). Metastatic disease was most common in Group 3 and Group 4 medulloblastomas (30 and 31%, respectively), while much lower in the Wnt group (9% of children) [6].
\nAlthough a biopsy specimen is required for definitive diagnosis of medulloblastoma, brain magnetic resonance imaging (MRI) with gadolinium is the preferred imaging modality to best characterize lesions suspected to be medulloblastoma. Brain MRIs allow for greater resolution of soft tissue with less interference from bone compared to computed tomography [12]. MRI findings associated with medulloblastoma can have varying enhancement patterns and intensities. Imaging can also identify areas of hemorrhage, calcification, or findings that suggest leptomeningeal metastasis [12]. It has been suggested that certain MRI findings may be more associated with certain histopathological subtypes [12].
\nOnce identification of suspected medulloblastoma has been made on imaging, a decision needs to be as to how tissue sample should be accessed. The current standard of care is to resect as much of the lesion as possible if able to do so in a safe manner [13]. If it is deemed unsafe to do so, a stereotactic biopsy of the suspected lesion would allow for a confirmatory pathologic diagnosis. Once tissue has been obtained, the patient must be reassessed and assigned to the standard-risk group or high-risk group which informs subsequent patient treatment regimen. The goal of this treatment regimen, which includes chemotherapy with or without chemoradiation, is to treat disease that may not have been fully resected by surgery.
\nIn order to place patients into one of these groups, additional imaging is required postoperatively, as well as cerebrospinal fluid (CSF) analysis and adequate pathologic specimen. Specifically, these two risk classifications are defined by size of residual tumor following resection and status of metastasis [14]. Standard-risk groups are less likely to have tumor recurrence following resection, while high-risk groups are more likely to have tumor recurrence.
\nStandard-risk medulloblastoma occurs in 70% of patients [15]. Although prospective randomized trials comparing radiotherapy alone to combined chemoradiation for treatment of standard-risk medulloblastoma have not been performed, combined therapy is currently the standard of care of standard risk medulloblastoma [16]. Patients in this risk group are typically treated with a combination of chemotherapy followed by radiation, although radiation therapy alone has been used [15, 17, 18]. Multiple protocols exist for the chemotherapeutic treatment of medulloblastoma. One chemotherapeutic regimen includes treatment with a combination of vincristine, cisplastin, lomustine, and cyclophosphamide alongside radiation therapy over about a 1-year period [15]. High-risk or unresectable tumors are also treated with chemoradiation. Infants (<3 years old) are typically not treated with radiation owing to intolerability of side effects.
\nRisk stratification of medulloblastoma patients has improved cure rates for high-risk cases and limited radiation therapy exposure in treatment regimen for standard-risk patients, thereby reducing side effects. Nevertheless, even with improved cure rates for patients, long-term sequelae of treatment remain a concern. Radiation therapy has been associated with long-term neurocognitive deficits, cytopenias, opportunistic infections, and secondary malignancies [15, 19]. Children are especially sensitive to the adverse effects of radiation therapy, and as such radiation doses for treatment are lower for pediatric than for adult patients [15].
\nLong-term chemotherapy too has known side effects that have been described extensively elsewhere and include neurocognitive impairment, hearing loss, endocrine perturbations, cardiac and respiratory conditions, and secondary malignancies [15, 20]. Moving forward, further studies need to be performed to optimize current treatment or to identify new therapeutics to minimize side effect profile. Classification of medulloblastoma subgroups, for instance, focuses research toward drug targets within molecular pathways driving these subgroups. These subgroups are described in detail below.
\nIn one trial of pediatric medulloblastoma, 10-year event free survival (EFS) and overall survival (OS) rates were 75 and 80%, respectively, for kids with standard-risk medulloblastoma treated with radiation followed by chemotherapy [21]. In another trial, 5-year EFS ranged from 65 to 70% in patients who received both chemotherapy and radiation following tumor resection [13]. Treatment with radiation therapy alone had survival rates 50–65% even with higher dose radiation [21, 22].
\nIn comparison to pediatric medulloblastoma literature, studies assessing the treatment of adult medulloblastoma are rare. One retrospective study of adult medulloblastoma treated with chemotherapy and craniospinal radiation identified a 4-year EFS of 68% [18]. Other studies have identified survival rates of 40–80% [23].
\nRelapses most likely occur within the first 2 years of diagnosis, with one-third occurring within the first 3–5 years [21]. Earlier relapses are more likely to be associated with metastatic disease [21], while later relapses (>5 years after diagnosis) were more likely to be related to local disease. The posterior fossa is the most common site of relapse. Relapses must be distinguished from secondary tumors. Secondary tumors can occur following radiation, either at sites of prior irradiation or at extracranial sites near sites of primary radiation (thyroid, bone, etc.). One study identified a 4.2% 10-year cumulative incidence of secondary tumors following treatment with chemoradiation [21]. Increased use of mutagenic chemotherapy has also been suggested to play a role in the increasing incidence of secondary tumors following treatment of medulloblastoma.
\nMolecular subgrouping of medulloblastoma plays an important role in prognosis. In brief, the Wnt subgroup demonstrates the most favorable prognosis, whereas Group 3 medulloblastomas present the worst. Other factors that may affect prognosis include stage and complete or incomplete resection of tumors [18].
\nThe World Health Organization has subdivided medulloblastoma into five distinct histopathologic categories [24]: classic, desmoplastic/nodular, medulloblastoma with excessive nodularity, anaplastic medulloblastoma, and large cell medulloblastoma (Figures 2 and 3). Certain histological subtypes predominate patient age groups: 71% of pediatric cases classify as classic medulloblastoma, whereas 57% of infant cases exhibit desmoplastic/nodular histology [25]. Large cell and anaplastic medulloblastomas are associated with a poor prognosis, whereas desmoplastic/nodular medulloblastomas usually demonstrate an excellent outcome [25].
\nMedulloblastomas are grouped histologically or molecularly. Left image shows MRI of a pediatric patient with a classical medulloblastoma. Right image shows MRI of an infant with medulloblastoma with extensive nodularity. Copyright © 2014 Faculty of 1000 Ltd, from
In addition to histological categories, retrospective molecular diagnostics have additionally allowed for medulloblastoma to be subdivided into four molecular subgroups (Table 1). The most well understood of these four subgroups are those medulloblastoma variants that involve the sonic hedgehog pathway (30% of patients with medulloblastoma and 60% of adults) and those involving the Wnt pathway (10% of all patients with medulloblastomas and 15% of adults) [26]. Molecular subgrouping may inform chemotherapy regimen, especially in light of emerging research about potential drug targets within involved molecular pathways.
\nHistological slides stained with hematoxylin and eosin of medulloblastomas showing heterogeneity across patient tissue samples. Images obtained with permission from Dr. Kay Ka Wai Li (Prince of Wales Hospital, Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong).
Wnt-type medulloblastoma is characterized by enhanced Wnt-β-catenin pathway activation [5] and tends to show classic histology rather than the poorer prognoses anaplastic or large cell type histology [6]. Among the medulloblastoma molecular subgroups, Wnt medulloblastoma is the least common, occurring in 10–15% of medulloblastomas [27]. It affects males 1.5 times more than females [6] and occurs rarely in infants (<3 years old).
\nFor reasons that have yet to be elucidated, medulloblastoma tumors carrying Wnt mutations carry a better prognosis than other subtypes. In fact, meta-analysis of medulloblastoma subgroups found an overall 10-year survival rate of 95% in children with Wnt medulloblastoma and 100% 5-year survival rate among adult Wnt medulloblastoma [6].
\nAll medulloblastomas with heightened nuclear staining of β-catenin are grouped into Wnt-type. β-Catenin is a key promoter of the Wnt pathway, an evolutionarily conserved pathway involved in cellular homeostasis and embryogenesis. The pathway is involved in central nervous system development; indeed, derangements of Wnt signaling have been described in diseases of the CNS, including neural tube defects, Williams syndrome, Alzheimer’s disease, and schizophrenia [28].
\nThe Wnt pathway classifies into the canonical pathway and two separate noncanonical pathways. The noncanonical Wnt pathways appear to be independent of β-catenin. The canonical pathway is β-catenin dependent and is characterized by interaction of a Wnt ligand with the extracellular domain of Frizzled, a G-protein-coupled receptor. This interaction results in accumulation of intracellular β-catenin, promoting downstream gene activation [29, 30]. Multiple genes and proteins have been identified as regulatory factors for this pathway. β-Catenin is an unstable protein, and in the absence of Wnt ligand, it is broken down by a degradation complex composed of multiple proteins, the tumor suppressor protein APC and the scaffolding protein AXIN [31] are among them.
\nNinety percent of the time, Wnt medulloblastoma is driven by mutation of β-catenin (
Alongside other evolutionarily conserved pathways [31] including the SHH and Notch pathways, the Wnt pathway has also been implicated in the development of cancer stem cells (CSCs), a subgroup of cancer cells defined by their pluripotency and capacity for self-renewal [29, 31]. The identification of cancer stem cells as a subgroup of pluripotent self-renewing cancer cells has led to the theory that they may be necessary for tumorigenesis. Aberrations in evolutionary conserved pathways, including the Wnt pathway, are frequently identified in cancer stem cells. The Wnt pathway therefore is an attractive means for targeting cancer stem cells, particularly in malignancies that are known to overexpress Wnt.
\nA number of molecules that interact with the Wnt pathway are currently being investigated as potential antitumor therapies in both preclinical studies and clinical trials. Tankyrase inhibitors have been identified that lead to downstream degradation of β-catenin [29]. JW55, a novel tankyrase inhibitor, has been shown in mice studies to reduce tumor development and colorectal cancer cell growth [32]. Inhibitors of Dishevelled, a protein that promotes downstream Wnt signal transduction, have also been shown to inhibit downstream Wnt signaling [33].
\nInterestingly, known nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to have anti-Wnt pathway activity, possibly explaining in part their antineoplastic properties [27, 34, 35].
There are a number of ongoing trials using novel agents targeting the Wnt pathway. These agents include PRI-724, designed by Prism BioLab and which blocks the interaction of β-catenin with cotranscriptional coactivator CBP [29, 31]. A Phase I clinical on the molecule LGK-794, a porcupine inhibitor that inhibits Wnt protein secretion, is currently recruiting patients and will assess the safety profile in patients who carry malignancies that are dependent on Wnt ligands [29, 31]. It is important to note that these Wnt pathway-targeting compounds have not been tested in medulloblastomas, which would be the next direction for assessing their efficacy in Wnt medulloblastoma. However, although the Wnt pathway is a potential target for future medulloblastoma therapies, some authors have described potential theoretical barriers to the utilization of Wnt-targeted therapy in malignancy [28]. First, the Wnt pathway is crucial to organogenesis and homeostasis, begging the question as to whether altering the Wnt pathway may be detrimental to these processes. Second, some have contested the assumption that Wnt pathway antagonism would be desirable as anticancer therapy, given that the Wnt pathway is involved in neural regeneration after brain injury (such as surgery). The ongoing clinical trials using therapies targeting the Wnt pathway will help to better elucidate the safety and viability of targeting this pathway.
\nClinical and molecular overview of medulloblastoma subgroups | \n|||
---|---|---|---|
Group | \nPatient epidemiology | \nPrognosis | \nAssociated genetic aberration | \n
SHH | \nFrequent in infants and in adults but not in pediatric and teenage patients | \n75% 5-year survival | \nsonic hedgehog signaling | \n
WNT | \nRare in infants More common in males than in females | \nBest prognosis of all subgroups: 95% 10-year survival in children; 100% 5-year survival in adults | \nβ-Catenin—increased MYC expression | \n
Group 3 | \nInfants and pediatric patients but rare in adults | \nWorst prognosis of all subgroups: 40–60% 5-year survival | \nMYC Photoreceptor-associated pathways | \n
Group 4 | \nMost prevalent subgroup, 34% of cases Found in all age groups | \n75% 5-year survival | \n17q chromosome Loss of X chromosome in female patients | \n
Summary of key aspects of the four molecular subgroups of medulloblastoma.
Activation of the sonic hedgehog (SHH) pathway drives tumorigenesis in the SHH group of medulloblastomas. SHH medulloblastomas are frequently found in infant (ages 0–3) and adult (>16 years) but occur less commonly in pediatric cases [25]. The prognosis is similar to Group 4 medulloblastomas.
\nIn sonic hedgehog signaling, the receptor Patch (specifically Ptch1) inhibits a G-protein-coupled receptor called Smoothened (Smo) in the absence of Hedgehog ligand. Hedgehog ligand binding to Patch results in disinhibition of Patch from Smo, allowing downstream signaling transduction and the activation of the Gli transcription factors, Gli1, Gli2, and Gli3 (Figure 4) [39, 40]. Mutations in Patch, Smo, Gli1, and Gli2 have been shown to initiate medulloblastoma in a variety of models [41–44]. Mutation in SUFU, a negative regulator of SHH signaling, is another initiating mutation [45].
\nSchematic showing sonic hedgehog (SHH) signaling: in the absence of Hedgehog ligand, the Patch receptor (Ptch1) inhibits Smoothened (Smo). Hedgehog ligand binding to Patch results in the disinhibition of Smoothened, leading to downstream activation of the Gli transcription factors. Schematic illustrated by author JYY of this book chapter.
Alkylating agents have long since served in chemotherapy for medulloblastoma, but for the SHH subgroup, inhibitors of Smo are also popular. The compound cyclopamine launched initial interest in targeting SHH signaling which was responsible for the developmental defects found in sheep that ingested corn lilies in which cyclopamine was originally discovered [46]. 2004 marked the year that Genentech identified the drug vismodegib in a screen for compounds that inhibit the SHH pathway [46]. Studies assessed vismodegib initially in advanced basal cell carcinoma and were also launched to assess the drug for other cancers [46]. Vismodegib was approved in 2012 by the Food and Drug Administration (FDA) for the treatment of metastatic or recurring BCC [46]. A Phase I study has been undertaken to assess the safety, safe dosing range, and side effects of vismodegib in a population of children with recurrent or refractory medulloblastoma [47]. Out of the 20 patients enrolled for flat-dosage testing (150 mg for smaller body area and 300 mg for larger), only two dose-limiting toxicities were observed. The study concluded that vismodegib is well tolerated in pediatric patients with recurrent or refractory medulloblastoma and recommended 150 or 300 mg dosage for Phase II trials.
\nConsequently, a Phase II trial was conducted at this recommended dosage with adult and pediatric patient groups. The study found that vismodegib increased progression-free survival in SHH medulloblastoma group but not in the non-SHH medulloblastoma group. Vismodegib exhibited activity against adult SHH medulloblastoma. However, inadequate sampling size for the pediatric group precluded conclusions about vismodegib efficacy in this group [48]. Therefore, vismodegib appears promising for adult medulloblastoma patients but remains to be further examined for pediatric patients.
\nIn 2015, the FDA approved another Smo inhibitor, sonidegib (also known as LDE225), for use in treating basal cell carcinoma [49]. Sonidegib has been tested in a variety of cancers, including medulloblastoma [50]. Other Smo inhibitors are being tested in other cancers. GANT61 has been tested in a prostate cancer model [51], while BMS-833923 was tested in a gastric and esophageal cancer model [52]. Both remain to be tested in medulloblastoma.
\nFor SHH medulloblastoma, targeting SHH signaling is a more direct therapeutic approach than the use of alkylating agents; however, drug resistance may pose a realistic concern. For example, it has been found that drug resistance can arise from amino acids changes in Smo which leads to a deficiency in drug binding to vismodegib [53]. With the approval of sonidegib, researchers then investigated whether its usage might improve tumor response in patients with basal cell carcinoma who were resistant to vismodegib. They concluded that, unfortunately, patients with advanced basal cell carcinoma, who were previously resistant to vismodegib, also experienced resistance with sonidegib treatment [54]. So, drug resistance with novel Smo inhibitors remains an ongoing concern.
\nToward the goal of developing combination therapies and limiting drug resistance, recent research has progressed to investigating the molecular regulation of proteins within the SHH pathway as potential drug targets. For example, several kinases have been shown to control the activity of Gli1: ribosomal protein S6 activates Gli1 through phosphorylation on its serine 84 [55], while protein kinase A phosphorylation inhibits Gli1’s activity [56].
\nAMP kinase (AMPK), a regulator of cell energy allocation during stress conditions, has been shown to modulate Gli1 activity. Specifically, overexpression of AMPK leads to a decrease in Gli1 expression, while downregulation of AMPK activity increases Gli1 expression [57]. Therefore, suppression of SHH signaling through downregulation of Gli1 may serve as a venue of targeting SHH medulloblastomas. Our group has demonstrated how direct regulation of SHH signaling through AMPK function impacts tumorigenesis. We found that AMPK regulates Gli1 activity by phosphorylating the transcription factor at serines 102 and 408 and threonine 1074. Mutation of these phosphorylation sites to nonphosphorylatable alanine increases Gli1 protein stability, transcriptional activity, and oncogenic potency, suggesting that AMPK phosphorylation reduces Gli1 activity (Figure 5). Another group has supported our finding that AMPK phosphorylates and may regulate Gli1 through serine 408. This group found that AMPK promotes Gli1 degradation upon its phosphorylation of serine 408 on Gli1 [58]. Further studies illustrating the effect of modulating the activity of Gli1 regulators on medulloblastoma tumorigenesis in
AMPK phosphorylation on Gli1 reduces Gli1 activity. During stress conditions, AMPK phosphorylation on Gli1 results in decreased cell growth. Uncontrolled Gli1 activity, which can arise from downregulating AMPK, leads to uncontrolled cell growth such as in medulloblastoma. Schematic adapted from author JYY’s work,
Another approach to developing combination drug therapies has been to identify additional signaling pathways that impact SHH-driven medulloblastoma. Research has demonstrated that these pathways play a role in medulloblastoma development:
\np53: Tumor suppressor p53 is highly mutated in pediatric medulloblastomas and is a significant factor in determining prognosis [6]. A cohort study found that 5-year survival rates differed between 41 and 82%, respectively, for SHH medulloblastoma cases with and without p53 mutations [59]. In mice, the incidence of medulloblastoma increases to nearly 100% with p53 loss [60]. Therefore, regulators of p53 activity might serve as highly attractive drug candidates for combination therapy with Smo inhibitors. For example, driving down levels of MDM2, a negative regulator of p53, has been shown to decrease expression of Gli1 and Gli2 [61].
cAMP: In general, researchers have discovered that the levels of second messenger cAMP are inversely correlated with tumor grade and growth. Ablation of the G protein Gαs is sufficient to initiate SHH medulloblastoma, and mice harboring the
TGF-β: Expression analysis of Ptch1 heterozygous and Smo/Smo mouse medulloblastoma tumors of varying clinical severities found a correlation between TGF-β expression levels and medulloblastoma progression. In general, it was found that activation of the TGF-β pathway correlated with better prognosis with patients [63]. For instance, positive nuclear staining of SMAD3, a downstream component of TGF-β signaling, was associated with longer patient survival [63]. Therefore, regulation of the TGF-β signaling pathway in conjunction with SHH signaling may be another venue of combination therapy.
Basic FGF: Overall, basic FGF (bFGF) signaling appears to have an inhibitory role on SHH-induced proliferation. The addition of bGFG to tumor cultures has been shown to limit tumor formation and proliferation and to inhibit expression of the transcriptional products of SHH signaling, namely
While these intersecting pathways contain possible targets, determining the exact mechanism by which they impact SHH medulloblastoma is the limiting step to uncovering the best candidates to target.
\nWhile Wnt and SHH medulloblastomas have been identified by mutations within these pathways, more comprehensive biological pathways have not been delineated for Group 3 and Group 4 medulloblastomas. Hence, these have been so named until the underlying biology is further elucidated.
\nConventional diagnosis of Group 3 medulloblastomas is accomplished through transcriptional profiling [3]. Group 3 medulloblastoma is associated with increased MYC expression and enrichment for photoreceptor pathway-associated genes; these genes are overexpressed in Group 3 [3]. In addition, Group 3 can be divided into subtype based on MYC expression. In Group 3α subtype, all patients contain MYC amplification and this is associated with poor prognosis with increased recurrence and mortality, while the Group 3β subtype contains no MYC amplification and has a prognosis similar to Group 4 medulloblastomas [3]. Medulloblastomas of this group are found in both infants and children, but rarely in adults, and are found more in males than in females [3]. Histologically, Group 3 medulloblastomas frequently have large anaplastic cell pathology [3].
\nWhile many details about the molecular makeup of Group 3 medulloblastomas remain unresolved, recent literature therapeutically targeting Group 3 medulloblastoma may reveal clues to the molecular pathways driving this subgroup. The folate synthesis inhibitor pemetrexed and nucleoside analog gemcitabine demonstrated a synergistic effect in increasing the survival of mice bearing MYC-overexpressing tumors [65]. The same drug combination had little effect on mice medulloblastomas of the SHH subgroup [65]. These observations are supported by gene set enrichment analysis showing that Group 3 medulloblastomas are enriched in the folate and purine metabolism pathways compared to Group 4 and SHH medulloblastoma [65].
\nThe antihelmintic drug, mebendazole, has been shown to inhibit angiogenesis in medulloblastoma [66]. While it acts as a microtubule synthesis inhibitor in worms, studies with medulloblastoma models suggest that it can inhibit vascular endothelial growth factor receptor 2 (VEGFR2) [66]. Targeting class I histone deacetylase 2 has also been shown to impact Group 3 medulloblastoma tumor cell viability [67].
\nThe International Cancer Genome Consortium (ICGC) PedBrain Tumor Project published in 2014 the analyses of deep sequencing of Group 3 and Group 4 tumors. This study uncovered novel information about the biology between this subgroup. Tetraploidy was a common event for both Group 3 and Group 4 tumors, respectively, and tetraploid tumors displayed signs of genomic instability [68]. With Group 3, the most frequently mutated gene was SMARCA4 [68]. Together, both
Group 4 is the most prevalent medulloblastoma subgroup, accounting for about 34% of all medulloblastomas [6]. A high frequency (66%) of isochromosome 17q is associated with Group 4 medulloblastomas [6]. Strikingly, 80% of women with Group 4 medulloblastoma also have X chromosome loss [6]. Group 4 medulloblastomas have a prognosis comparable to SHH group medulloblastomas [6].
\nThe ICGC PedBrain Project found that KDM64, a histone 3 lysine 27 demethylase, was mutated in 10% of Group 4 tumors [68]. These mutations reveal the genetic and molecular pathways that go awry in Group 3 and Group 4 tumors. For example, the ICGC PedBrain uncovered an association between TBR1 and Group 4 medulloblastomas [68]. TBR1 is a T-box transcription factor shown to play a role in brain development. Of particular interest is the gene CTDNEP1, found mutated in 10% of Group 4 tumors and which is located on 17q [68]. CTDNEP1 encodes a nuclear membrane phosphatase and in mammals is shown to play a role in nuclear membrane biogenesis and in lipid activation. As 66% of Group 4 medulloblastomas contain 17q, mutations found on this isochromosome are particularly important for study.
\nClearly, with respect to Group 3 and Group 4 medulloblastomas, further studies about the molecular basis for these subgroups are needed. These two subgroups pose great clinical challenges: Group 4 is the most prevalent group, while Group 3 has the poorest diagnosis. Yet a dearth of knowledge about the molecular basis behind each group limits drug targeting. The growing body of studies which include genome-wide mining for enrichments within each subgroup along with
Currently, there are a number of clinical trials evaluating the safety and efficacy of Wnt-targeted therapies in patients with other malignancies that overexpress the Wnt pathway; however, none of these are being tested in medulloblastomas. The efficacy of these agents in treating Wnt medulloblastoma remains to be assessed. Additionally, in light of the high survival rates of standard risk patients with Wnt medulloblastoma, additional studies would be helpful to identify optimal treatment regimens that will maintain these high survival rates while minimizing treatment side effects.\tWith respect to SHH-driven medulloblastoma, identification of novel targets especially for combination drug therapy will address the concern for drug resistance and limited efficacy of current treatments. For example, the identification and assessment of novel Gli inhibitors for SHH-mediated cancers should be evaluated in the context of medulloblastoma. In addition, the effects of the crosstalk of intersecting pathways on medulloblastoma tumorigenesis should be further studied.
\nPerovskite solar cells (PSCs) have received a great deal of attention in the past few decades due to their impressively high power conversion efficiency (PCE) [1]. To date, PCE as high as 25.6% has been successfully recorded. This performance has already been compared with the single-crystalline silicon solar cells system. With the advancement in the perovskite properties control, including the crystallinity properties, grain size, and stability properties, further improvement in the PCE is expected to be achieved soon. The continuous growth in the preparation of the high-performance charge selective layer in the perovskite solar cells further contributes to the rapid progress in the PCE improvement of the PSC [2].
Along with the transparent conducting electrode (TCE) and the top metal contact, a PSC device is composed of an electron-transport layer (ETL), an organometal-halide perovskite active layer, and a hole-transport layer (HTL). In these solar cells, the perovskite and its photoelectrical properties are the keys to the overall photovoltaic process. Its unique high-optical absorption constant drives massive photon absorption and exciton generation in the device. Despite this key fact, the carrier transport and interfacial charge transfer dynamics play another crucial factor for the generation of the overall PSC performance. These two parameters depend on the nature of the surface and the crystallinity properties of the charge-selective layers [3].
One of the serious problems in perovskite solar cell devices is the loss of charge carriers during the transport process in the carrier layer. This is because, the carrier layer has low crystallization, high grain boundary resistance as well as experiences loss of carrier charge during extraction to the outer electrode. The main factor of carrier charge lost during extraction to the outer electrode is due to the high interface resistance between the electrode and the carrier layer. Therefore, it is expected that when a carrier layer that has high crystallinity, very low thickness, and good coupling conditions with external electrodes is used, then the performance of the device will increase.
The electron transport layer (ETL), for example, TiO2, and other semiconducting oxides, such as SnO2, ZnO, have been widely applied in the perovskite solar cells fabrication. Despite the excellent performance demonstrated by them, this ETL suffers from large-density surface defects related to oxygen vacancy, particularly in the TiO2 system. The defect from such vacancy causes immense trap-limited (Shockley-Read-Hull) transport in the extraction of the photogenerated carrier to the external electrode. This in many cases degrades the photovoltaic performance of the PSC up to a certain degree, reducing the power conversion efficiency of the device. Even though there exist several methods in the passivation of such defects, such as acid passivation, etc., the improvement is minute. In addition, this method may add additional resistance to the photocarrier transport reducing the power conversion efficiency. Along with these crucial factors, the crystallinity properties of the ETL add an additional issue to the photocarrier transport dynamic in the device. As normal in the high-performance PSC fabrication, mesoporous TiO2 or SnO2 was used as ETL along with a compact layer of TiO2 or SnO2 (See Figure 1), [4]. As the figure reveals, the mesoporous layer is composed of a large number of interconnected small grain particles that produce grain boundary resistance due to lattice mismatch among the connected particles. This resistance should be massive due to their large-scale existence on the layer. This certainly complicates the transport of photogenerated electrons to the electrode layer, such as high internal resistance or radiationless recombination [5, 6]. Therefore, the selection of the right material for the carrier layer is important in determining the performance of a device. Such resistance boundary further augments the presence of mesoporous-compact layer interface resistance in the ETL system of the PSC. From this picture, we can estimate the loss would be suffered by the device during the photovoltaic process. This means that if such ETL is replaced with the single-crystalline ETL system, the performance of the perovskite solar cells can be improved.
Mesoporous TiO2 ETL. (A and C) Top and side view of mesoporous TiO2 layer on compact layer TiO2. (B and D) Top and side of mesoporous TiO2 layer. (Reprinted from [
Recently, materials of two-dimensional (2D) dichalcogenide transition metals (TMDs), such as MoS2, WS2, TiS2, CdTe, and others, have been used as carrier layers in perovskite solar cells due to their high charge carrier mobility, unique optoelectrical properties, large exciton binding energy, very fast interface charge transfer properties as well as excellent physical and chemical stability properties [7]. Their optoelectronic properties were also found to correspond to the number of layers, dopants, and strains (straining). The phenomenon of the massive charge transfer process in these van der Waals crystals driven by the collective motion of excitonic surfaces enables a high interfacial charge extraction and reduces charge recombination for an effective photovoltaic process [8]. One of the uniqueness of the TMDs layer is that it has an atomic-scale thickness (very thin) and has high crystallinity. With its planar (2D) structure, it will produce a strong coupling when grown on the electrode surface. Therefore, it has great potential for a carrier layer in perovskite solar cells.
Transition metal dichalcogenide (TMD) has the chemical formula of MX2 where M is the transition metal from groups 4 to 10 in the periodic table system, and X is a chalcogen atom such as sulfur (S), selenium (Se), or tellurium (Te). Figure 2 shows the typical structure of TMD. The structure has two layers of chalcogen that clamp a transition metal layer making this material have its uniqueness in electronic, optoelectronic properties, and chemical stability [10]. The electronic and optical properties of TMDs materials change significantly depending on the number of layers. For example, the MoS2 band gap increases from 1.29 eV (multilayered MoS2) to 1.59 eV (monolayer MoS2), and also this bandgap changes from an indirect bandgap to a direct bandgap as the number of layers decreases [11].
Typical structure of transition metal dichalcogenide materials. (A) Typical layer stacking structure in bulk transition metal dichalcogenide structure. T and X represent the transition metal and chalcogen elements, respectively. (B) Top and side view of single-layer of TMD with 2H-phase. (C) Side view of single-layer TMD with 1T-phase. (Reprinted from [
As is well known, most of these 2D TMD materials have ambipolar properties that enable the materials to transport both electrons and holes [12]. In other words, this allows 2D TMDs material to be used as ETL or HTL in n-i-p or p-i-n perovskite solar cells. However, most perovskite solar cell applications use these 2D TMD materials as HTL. Only MoS2 and TiS2 have been used as ETLs and have successfully produced efficiencies as high as 13.14% and 18.79% [7, 13]. Table 1 shows several PSC device structures utilizing TMD as ETL. Recently, there was a first simulation study on the photoelectric properties of WS2 as an ETL in perovskite solar cells reported with efficiencies as high as 25.70% [23]. By having high electron mobility as well as energy levels appropriate to the perovskite layer, the WS2 atomic layer is expected to function as an ETL capable of producing high-performance perovskite solar cell devices.
Material | Device structure | PCE (%) | Ref. | |||
---|---|---|---|---|---|---|
TiS2 | FTO/TiS2/MAPbI3/spiro-OMeTAD/Au | 23.38 | 1.05 | 0.71 | 17.37 | [14] |
TiS2 | ITO/TiS2/ FAxMA1-xBrxClyI1-x-y/spiro-OMeTAD/Ag | 24.68 | 1.00 | 0.75 | 18.79 | [7] |
MoS2 | FTO/MoS2/MAPbI3/spiro-OMeTAD/Au | 21.70 | 0.89 | 0.63 | 13.14 | [15] |
MoS2 | ITO/MoS2/Csx(MAyFA1-y)1-xPb(IzBr1-z)3/spiro-OMeTAD/Au | 16.24 | 0.56 | 0.37 | 3.36 | [16] |
MoS2/TiO2 | ITO/TiO2/MoS2/MAPbI3/spiro-OMeTAD/Au | 13.36 | 0.65 | 0.51 | 4.43 | [17] |
MoS2/SnO2 | ITO/SnO2/MoS2/FAxMA1-xBrxClyI1-x-y/spiro-OMeTAD/Ag | 24.57 | 1.11 | 0.79 | 21.73 | [18] |
MoS2 | Graphene/MoS2/MAPbI3/PTAA/Au | 20.92 | 0.91 | 0.76 | 14.42 | [19] |
MoS2 | ITO/MoS2/MAPbI3/PCBM/Al | 12.50 | 0.85 | 0.57 | 6.01 | [20] |
SnS2 | ITO/SnS2/MAPbI3/Spiro-OMeTAD/Au | 23.70 | 0.95 | 0.61 | 13.63 | [21] |
SnS2 | ITO/SnS2/MAPbI3/Spiro-OMeTAD/Au | 21.70 | 1.011 | 0.60 | 13.20 | [22] |
Photovoltaic parameters of perovskite solar cell devices using dichalcogenide transition metals (TMDs) as ETLs.
TiS2 is one of the TMDC family that has been intensively studied recently due to its semi-metallic properties with low-bandgap value, i.e., 0.2 eV. With high electrical conductivity, i.e., 1 x 104 S m−1, this material is potential as an electrode in many applications including lithium-ion batteries and solar cells. Despite its excellent electrical properties, the use of TiS2 as independent electrode material in the application is limitedly demonstrated. It is mainly stacked with other materials such as MoS2 [24] or TiO2 to improve the properties in applications. For the case of MoS2 stacked with TiS2, the TiS2 can form Schottky contact with MoS2 with barrier height [24] between these two atomic layers can be varied by the doping type and concentration either in the MoS2 or TiS2 side (Figure 3). This certainly provides a wider opportunity to modify the electrical properties of the system for desired performance in application. In the typical process, n-type-doped TiS2–MoS2 (ML) contacts exhibit a barrier height relatively larger, i.e., 1.0 eV below doping level degeneracy. Nevertheless, these n-type-doped contacts still have the potential as the switch in high-power as well as tunnel Schottky barrier MOSFETs. In contrary to the n-type doped system, the p-type-doped TiS2–MoS2 (ML) exhibits a zero barrier height at a particular doping concentration, i.e., 5 × 1018 cm−3. Under this condition, the depletion region width is zero and the band becomes flat, revealing that the contact is ohmic and the barrier height is small. These results reveal the unique unusual interfacial properties arising from this ultimate thin contact that promise a special function in the application. This phenomenon could be the driving factor for an efficient photocarrier extraction in the perovskite solar cells using ETL modified with MoS2 or TiS2 atomic layer.
PLDOS of TiS2–MoS2 (ML) FET-like junctions doped with different doping concentrations and the variation of band structure at interface B. a–d The doping concentrations are: N = 5 × 1019 cm−3, N = 1 × 1019 cm−3, N = 5 × 1018 cm−3, and P = 5 × 1018 cm−3. The thickness of TiS2 is four layers. On the right side, the plot shows the variation of band structure under different doping concentrations. The scale bar is from 0.0 to 90.0 (1/eV). Interface A is the interface between TiS2–MoS2. (Reprinted from [
For example, in the perovskite solar cells system with SnO2 ETL (Figure 4), there is an increase in the energy band alignment between the ETL and perovskite layer when the 2D TiS2 is attached to the surface of SnO2 [18]. The conduction band level of ETL (SnO2) reduced from 4.68 to 4.63 eV in the presence of 2D TiS2. This has narrowed the offset energy between the ETL and perovskite (conduction band level at 4.36 eV). As the result, the photogenerated carrier extraction becomes enhanced, improving the photocurrent and the power conversion efficiency. As shown in Figure 4C–4F, the power conversion efficiency increases from 19.65% to 21.73% when the SnO2 ETL is modified with the 2D TiS2 atomic layer. The nature of interfacial photocarrier dynamic improvement in the presence of the 2D TiS2 atomic layer can be seen from the increase of the
(A) Cross-sectional SEM image of the PSC. (B) The energy level diagram. (C) Representative J-V curves of the PSCs with SnO2 or SnO2 /2D TiS2 as ETLs. (D) EQE curve and integrated current density of the PSC with SnO2 /2D TiS2 as the ETL. (E) Histogram of the PCE of PSCs with SnO2 and SnO2 /2D TiS2 as ETLs analyzed from 25 cells. (F) Steady-state efficiency of the PSCs with SnO2 and SnO2/2D TiS2 as ETLs measured under constant voltages of 0.86 V and 0.92 V, respectively. (Reprinted from [
Figure 5 explains in detail how the photocarrier dynamic in the device was impressively modified in the presence of a 2D TiS2 atomic layer on the surface of SnO2 ETL. As presented, the photocurrent is enhanced impressively. This is the result of enhanced interfacial charge transfer as indicated by the transient and steady-state photoluminescence analysis result, which is also supported by the electrochemical impedance spectroscopy result, showing decrease in the interfacial charge transfer resistance in the device.
Comparison of SnO2 and SnO2/2D TiS2 as ETLs in PSCs: (A)
We also in our recent result have coupled the TiS2 atomic layer on top of the TiO2 surface to compensate for surface defect due to the oxygen vacancy, enhancing the interfacial charge transfer and transport dynamic when applied as ETL in perovskite solar cells [25]. The perovskite solar cells’ performance improves from 18.02 to 18.73% (Figure 6). Electrochemical impedance analysis revealed that there is an improvement as high as 13% in interfacial charge transfer in the ETL with 2D TiS2 and 43% improvement in the charge recombination resistance (Figure 7A). The latter is verified by the increase in the photocurrent (Figure 7B) and the decrease in the leakage current of the device when 2D TiS2 passivates the TiO2 surface (Figure 7C). We can relate this process to the reduction in the trap density in the device as shown by the value of
Photovoltaic performance of the 2D TiS2-TiO2 NG and TiO2 NG-based PSC. (A) Schematic structure of 2D TiS2-TiO2 NG-based PSC. (B)
Photoelectrical properties of the PSC device. (A) Electrochemical impedance spectra and equivalent circuit of the device. (B) Photogenerated current of the PSC device (
MoS2 atomic layer is the most studied TMD system because of its excellent optical and electrical properties [26, 27, 28] and has been used widely in perovskite solar cells as a hole-transport layer (HTL) and an electron-transport layer (ETL) [11, 15, 26] in the form of colloidal or flakes thin film [15, 28, 29, 30]. Table 1 lists down several perovskite solar cells using MoS2 as ETL with a particular device configuration. For example, Singh, Giri, et al. [13] have obtained power conversion efficiency as high as 13.2% from PSC devices using MoS2 material as ETL. In this study, they synthesized the MoS2 film directly on FTO substrate using microwave irradiation-assisted reduction method. It is found that the efficiency obtained by MoS2 material is close to the efficiency value obtained from TiO2 and SnO2 material making MoS2 material comparable to other ETL materials. Abd Malek et al. [16] have also developed different structures of MoS2 ETL on the ITO substrate. Instead of colloidal or flake structured film, an ultrathin layer of MoS2 prepared from ultrasonic spray pyrolysis was fabricated to obtain its functionalities as ultrathin ETL in the PSC device. The result showed that the PCE device performance depended on the condition during the preparation of the MoS2 atomic layer, particularly the substrate temperature. It is demonstrated that substrate temperature of 200°C is suitable for growing high-quality MoS2 atomic layer on ITO surface, thus, optimizing the power conversion efficiency of the PSC (Figure 8). This MoS2 thin-film-based device as ETL has shown high-stability properties where its efficiency can be maintained as much as 90.24% of the original efficiency after 80 s exposure continuously under simulated solar light illumination (AM1.5).
The photovoltaic parameter for MoS2 as ETL in PSC. (A) Schematic structure of the PSC device. (B) The
In addition to being used singly in the ETL, TMD materials can also be combined with other organic or inorganic electron transport materials to form electron transport materials. For example, Ahmed et al. [31] have added a MoS2 layer on top of the TiO2 layer to be used as ETL in perovskite solar cells. The use of MoS2/TiO2 as ETL has successfully increased the efficiency of the device by 16% higher than the device that only uses TiO2 as ETL. Similarly, Huang et al. [18] have successfully produced an n-i-p type plane device using SnO2 and 2D TiS2 as ETL. High efficiency was recorded by this group, which was as high as 21.73% with a relatively small hysteresis value. The increase in efficiency in this device is due to the matching of the ETL energy level and the appropriate perovskite layer as well as the lack of electron trap density in the ETL.
Tungsten disulfide (WS2) share common basic properties of TMD with other systems, such as high-mobility properties, unique optoelectronic properties, large exciton-binding energy, and good physical and chemical stability as well as ambipolar properties [11]. In addition, WS2 has an energy level that is suitable for the perovskite layer of three types of cations (Figure 9) and can be easily synthesized by the ultrasonic spray pyrolysis method. WS2 also has high stability as well as having fast interface charge transfer properties [32]. Among the available 2D TMD, the energy band structure of WS2 is a much better match with the common perovskite of MAPbI3 (Figure 10). Furthermore, it also has a relatively larger bandgap if compared with the other system in this class of materials, promising facile excitonic separation during the photovoltaic process and producing better power conversion efficiency.
Energy levels of dichalcogenide transition metal materials (TMDs) as ETLs and MAPbI3 as perovskite layers in perovskite solar cells.
Energy level diagram for n-i-p perovskite solar cells using WS2 ETL.
Recently, we have realized the PSC device utilizing the WS2 layer as ETL and evaluated how the number of layers of WS2 influences the carrier dynamic in the device [5]. We prepared the WS2 atomic layer via ultrasonic spray pyrolysis. Figure 11 shows a schematic diagram of the 2D atomic layer preparation. A modified commercially available ultrasonic spray system (Daiso, Japan) was used. A homemade solution container was placed on the top of the ultrasonic membrane of the system (Figure 11). Ultrasmall solution precursor mist can be produced from the process and fall on the ITO substrate surface that is positioned approximately 5 cm below the membrane. The temperature of the substrate was set at 350°C.
Schematic diagram of ultrasonic spray pyrolysis for the preparation of TMD ETL.
The typical morphology of the WS2 atomic layer on the ITO substrate is shown in Figure 12A. The WS2 nanosheet’s morphology resembles a circular structure that is produced from the precursors’ mist that emerged from the ultrasonic spray membrane. Confocal Raman imaging further indicated the existence of a very thin layer of structure from the circular structure as shown in Figure 12B. Raman analysis then confirmed the phase crystallinity of the WS2 (Figure 12C). As the figure reveals, there are two sharp peaks obtained from the Raman spectrum that is centered at 348.9 cm−1and 412.3 cm−1, which are associated with the in-plane (E2g) and the out-of-plane (A1g) vibration modes of the lattice (see inset in Figure 12C) [33, 34, 35, 36, 37, 38, 39]. According to the value of the separation between these two peaks, the thickness of the atomic layer is estimated to be in the range of 10 L. The X-ray diffraction analysis further confirmed the phase crystallinity of the WS2 layer (Figure 12D) [40, 41, 42]. The high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) analysis results (Figure 12F and G) show that the sample is single crystalline. However, the presence of SAED composed of a triple spot is related to the stacking of the WS2 atomic layer during the transfer to the lacey grid for HRTEM analysis. The XPS analysis then further confirmed the Raman and XRD analysis results on the phase crystallinity of the sample of which it belongs to WS2 (Figure 12H–I).
The morphology, phase crystallinity, chemical state properties of WS2 nanosheet. (A) FESEM image of WS2 nanosheet on the ITO substrate. (B-C) Raman imaging and spectrum of WS2 were obtained using 532 nm laser excitation. The inset in (C) shows the corresponding main vibration mode of Raman. (D) XRD spectrum for WS2 nanosheet showing 2H phase. (E-F) Low and high-resolution TEM image of WS2 nanosheet. (G) SAED pattern of WS2 nanosheet showing at least three stacking WS2 nanosheets. (H-I) High-resolution scan of XPS at W and S binding energy of WS2 nanosheet. (Reprinted from [
PSCs device was fabricated using the WS2 atomic layer as ETL and investigated how the thickness of the WS2 ETL influenced the photovoltaic process. The structure of the PSC device is ITO/WS2 nanosheets/Perovskite/Spiro-OMeTAD/Au. Perovskite used was triple cations system of Cs0.05[MA0.13FA0.87]0.95Pb (I0.87Br0.13)3 [43].
It was found that the thickness, represented by the number of layers, of the WS2 atomic layer ETL, strongly influences the power conversion efficiency of the PSC device (Figure 13). The results show that the PCE performance improves with the increase of thickness from 4 L to the optimum thickness of 7 L (WS30 sample in the figure). The optimized WS2 ETL thickness can produce a PSC device with PCE as high as 18.21% with
The photovoltaic performance of PSC using different thicknesses of WS2 ETL. (A)
To understand the extent effect of the WS2 atomic layer as ETL in the PSC device, the device performance was compared with the reference PSC utilizing well-known SnO2 ETL. In the typical process, the performance of SnO2-based PSC shows lower performance than the WS2 atomic layer–based device (Figure 14). Steady-state and transient photoluminescence analysis revealed that the interfacial charge transfer from the perovskite to ETL is high in the WS2 atomic layer [45], the result of optimized coupling due to ultra-flat surface morphology offered by the WS2 atomic layer. This phenomenon is further confirmed by the electrochemical impedance spectroscopy analysis result where it is obtained that the interface charge transfer resistance is lower in the WS2-based PSC device than the SnO2-based device. Thus, it can be remarked that the WS2 atomic layer enables highly active interfacial charge transfer for a high-performance PSC device.
The comparison of the photovoltaic parameter between WS2 (7 L, WS30 sample) and SnO2-based PSC device. (A)
2D atom thick TMD promises facile charge extraction and transport in the perovskite solar cells due to its ultimate thin and single-crystalline nature. The optimization of the 2D TMD layer to obtain a large dimension on the substrate surface is necessary to further promote a highly dynamic photogenerated carrier in the perovskite solar cells device. These materials may become a potential platform for high-performance perovskite solar cells.
We acknowledged the financial support from the Universiti Kebangsaan Malaysia for supporting this project under GUP-2019-071 and DIP-2021-025.”
The authors declare no conflict of interest.
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The equipment required to perform the distillation process is known as distillation column. Since initial investment and maintenance costs for distillation columns are very high it is necessary to have an appropriate mathematical model that allows improving the comprehension of the column dynamics, especially its thermal behaviour, in order to enhance the control and safety of the process. This chapter presents a general panorama of the mathematical modelling of distillation columns, having as a specific case of study the comparison of a space-state non-linear model and a Takagi-Sugeno fuzzy model for a batch distillation column using a binary mixture (Ethanol-Water).",book:{id:"5452",slug:"distillation-innovative-applications-and-modeling",title:"Distillation",fullTitle:"Distillation - Innovative Applications and Modeling"},signatures:"Adriana del Carmen Téllez-Anguiano, Mario Heras-Cervantes, Juan\nAnzurez-Marín, Gerardo Marx Chávez-Campos and José Antonio\nGutiérrez Gnecchi",authors:[{id:"12387",title:"Dr.",name:"Jose Antonio",middleName:null,surname:"Gutierrez Gnecchi",slug:"jose-antonio-gutierrez-gnecchi",fullName:"Jose Antonio Gutierrez Gnecchi"},{id:"189166",title:"Dr.",name:"Adriana",middleName:null,surname:"Téllez-Anguiano",slug:"adriana-tellez-anguiano",fullName:"Adriana Téllez-Anguiano"},{id:"194844",title:"MSc.",name:"Mario",middleName:null,surname:"Heras-Cervantes",slug:"mario-heras-cervantes",fullName:"Mario Heras-Cervantes"},{id:"194845",title:"Dr.",name:"Juan",middleName:null,surname:"Anzurez-Marín",slug:"juan-anzurez-marin",fullName:"Juan Anzurez-Marín"},{id:"194846",title:"Dr.",name:"Gerardo",middleName:"Marx",surname:"Chávez-Campos",slug:"gerardo-chavez-campos",fullName:"Gerardo Chávez-Campos"}]},{id:"54078",title:"Distillation Techniques in the Fruit Spirits Production",slug:"distillation-techniques-in-the-fruit-spirits-production",totalDownloads:4991,totalCrossrefCites:15,totalDimensionsCites:26,abstract:"During the distillation of the fermented fruit mash or juice, ethanol and water are the carriers of a huge number of the other volatile aroma compounds. Unique and distinctive flavour of the final spirits depends on their quantity and quality. Fruit spirits have higher concentration of almost all types of volatile compounds with comparing to other types of distilled spirits. The art of distillation run is to obtain the best balance between congeners present. Two different types of distillation equipment are used for the production of fruit spirits: copper Charentais alembic and batch distillation columns. Although both distillation methods are based on the same theoretical principles, a different quantity of the flavour compounds of the final spirits is produced by using different distillation equipment. The main difference was shown in different distributions of the methanol, n-propanol, higher alcohols and fatty acid esters. Distillation methods need to be adjusted for each fruit spirits regardless to distillation equipment employed because fermented mash of different fruit varieties has a different requirement for distilling. Alembic stills yield better aroma and more characteristic fruit distillates but are slow and require more labour. Column still cleans the distillate giving a decent aroma and higher concentration of alcohol.",book:{id:"5452",slug:"distillation-innovative-applications-and-modeling",title:"Distillation",fullTitle:"Distillation - Innovative Applications and Modeling"},signatures:"Nermina Spaho",authors:[{id:"189124",title:"Associate Prof.",name:"Nermina",middleName:null,surname:"Spaho",slug:"nermina-spaho",fullName:"Nermina Spaho"}]},{id:"54676",title:"Fractional Distillation of Organic Liquid Compounds Produced by Catalytic Cracking of Fats, Oils, and Grease",slug:"fractional-distillation-of-organic-liquid-compounds-produced-by-catalytic-cracking-of-fats-oils-and-",totalDownloads:1749,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"This work aims to investigate the fractional distillation of organic liquid products (OLP) obtained by catalytic cracking of palm oil (Elaeis guineensis Jacq.) at 450°C, 1.0 atm, with 5, 10, and 15% (wt) Na2CO3, using a stirred tank reactor of 143 L. The fractional distillations of OLP were carried out in laboratory scale with and without reflux using columns of different heights, and a pilot‐packed distillation column with internal reflux. OLP and distillation fractions (gasoline, kerosene, light diesel, and heavy diesel) were physicochemically characterized for density, kinematic viscosity, acid value, saponification value, refractive index, flash point, and copper strip corrosion. The OLP and light diesel fractions were analyzed by Fourier transform infrared spectroscopy (FT‐IR) and gas chromatography‐mass spectrometry (GC‐MS). For the experiments in laboratory scale, the yields of distillates decrease along with column height, with and without reflux, while those of bottoms products increase. The yields of distillates and gas increase with increasing Na2CO3 content, while those of bottoms products decrease. The densities of gasoline, kerosene, and light diesel produced in laboratory scale with reflux superpose exactly those of kerosene, light diesel, and heavy diesel produced in laboratory scale without reflux. The kinematic viscosity decreases with increasing column height for the experiments in laboratory scale. The acid values of distillation fractions decrease along with the column height for the experiments with and without reflux. The FT‐IR of distillation fractions in pilot and laboratory scales identified the presence of aliphatic hydrocarbons and oxygenates. The GC‐MS analysis identified OLP composition of 92.84% (area) hydrocarbons and 7.16% (area) oxygenates. The light diesel fraction contains 100% hydrocarbons with an acid value of 0.34 mg KOH/g, proving the technical feasibility of OLP de‐acidification by the fractional distillation process.",book:{id:"5452",slug:"distillation-innovative-applications-and-modeling",title:"Distillation",fullTitle:"Distillation - Innovative Applications and Modeling"},signatures:"C. C. Fereira, E. C. Costa, D. A. R. de Castro, M. S. Pereira, A. A.\nMâncio, M. C. Santos, D. E. L. Lhamas, S. A. P. da Mota, M. E. Araújo,\nLuiz E. P. Borges and N. T. 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",coverUrl:"https://cdn.intechopen.com/series/covers/3.jpg",latestPublicationDate:"May 13th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:8,editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. 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