Advantages and disadvantages of electric drive technologies.
\\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.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
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.
\n\n\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9364",leadTitle:null,fullTitle:"New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review",title:"New Insight into Cerebrovascular Diseases",subtitle:"An Updated Comprehensive Review",reviewType:"peer-reviewed",abstract:"“Brain circulation is a true road map that consists of large extended navigation territories and a number of unimagined and undiscovered routes.” \nDr. Patricia Bozzetto Ambrosi\nThis book combines an update on the review of cerebrovascular diseases in the form of textbook chapters, which has been carefully reviewed by Dr. Patricia Bozzetto Ambrosi, Drs. Rufai Ahmad and Auwal Abdullahi and Dr. Amit Agrawal, high-performance academic editors with extensive experience in neurodisciplines, including neurology, neurosurgery, neuroscience, and neuroradiology, covering the best standards of neurological practice involving basic and clinical aspects of cerebrovascular diseases. Each topic was carefully revised and prepared using smooth, structured vocabulary, plus superb graphics and scientific illustrations. In emphasizing the most common aspects of cerebrovascular diseases: stroke burden, pathophysiology, hemodynamics, diagnosis, management, repair, and healing, the book is comprehensive but concise and should become the standard reference guide for this neurological approach.",isbn:"978-1-78985-360-5",printIsbn:"978-1-78985-359-9",pdfIsbn:"978-1-78985-099-4",doi:"10.5772/intechopen.84327",price:139,priceEur:155,priceUsd:179,slug:"new-insight-into-cerebrovascular-diseases-an-updated-comprehensive-review",numberOfPages:356,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"bb9cf94a9674571e55f6e01a20ec372a",bookSignature:"Patricia Bozzetto Ambrosi, Rufai Ahmad, Auwal Abdullahi and Amit Agrawal",publishedDate:"May 13th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/9364.jpg",numberOfDownloads:14313,numberOfWosCitations:1,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:15,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 22nd 2019",dateEndSecondStepPublish:"April 29th 2019",dateEndThirdStepPublish:"June 28th 2019",dateEndFourthStepPublish:"September 16th 2019",dateEndFifthStepPublish:"November 15th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"221787",title:"Dr.",name:"Patricia",middleName:null,surname:"Bozzetto Ambrosi",slug:"patricia-bozzetto-ambrosi",fullName:"Patricia Bozzetto Ambrosi",profilePictureURL:"https://mts.intechopen.com/storage/users/221787/images/system/221787.jpg",biography:"Prof. Dr. Patricia Bozzetto Ambrosi graduated in Medicine from the University of Caxias do Sul, Brazil, and the University of Rome Tor Vergata, Italy. She is a former researcher in morphophysiology at the University of Córdoba/Reina Sofia Hospital, Spain. She graduated in Neurology/Neurosurgery at the Hospital of Restaura, SES, Brazil, and in Neuroradiology/Radiodiagnostics at Paris Marie Curie University, France. She holds a master’s degree in Medicine from the University of Nova Lisboa, Portugal, and one in Behavioral Sciences and Neuropsychiatry from the University of Pernambuco, Brazil. She also has a Ph.D. in Biological Sciences from the University of Pernambuco/Paris Diderot University. She is a former fellow in Interventional Neuroradiology at the Ophthalmological Foundation Adolphe de Rothschild, Beaujon Hospital, and Hospices Civils de Strasbourg, France. She was a praticien associe in Interventional Neuroradiology at Neurologique Hospital Pierre Wertheimer, University of Lyon Claude Bernard, France, and a visiting professor at the University of Paris Diderot-Neuri Beaujon. She is an independent consultant/supervisor in neuroradiology, neuroendovascular, and imaging and a clinical professor of medicine. She has been an academic collaborator researcher in the Cardiovascular Department, University of Leicester, England. Dr. Ambrosi has experience in innovative research for the development of new technologies and neurosciences and is an academic editor and reviewer of several scientific publications about neurological diseases.",institutionString:"Independent Neuroradiologist and Neurologist Consultant",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Paris Diderot University",institutionURL:null,country:{name:"France"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"289495",title:"Dr.",name:"Rufai",middleName:null,surname:"Ahmad",slug:"rufai-ahmad",fullName:"Rufai Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/289495/images/13032_n.jpg",biography:"Dr. Rufai Yusuf Ahmad graduated with a BSc in Physiotherapy from Bayero University, Kano, Nigeria, in 2001. He obtained his MSc and PhD in Health and Rehabilitation from the University of Southampton, UK, in 2008 and 2012, respectively. He also received his Doctor of Physiotherapy degree from the Michigan-Flint University, USA, in 2015. Dr. Ahmad is Associate Professor and Deputy Director (Procurement and Training), Directorate of Laboratory Management at Bayero University, Kano, and an Honorary Consultant Physiotherapist at Aminu Kano Teaching Hospital, Kano. He is a former Head of Department of Physiotherapy, Deputy Dean, Faculty of Allied Health Sciences, Bayero University, and editor-in-chief of the Bayero Journal of Evidence-Based Physiotherapy. He is currently the National President of the Nigeria Society of Physiotherapy and a member of the Medical Rehabilitation Therapists Board of Nigeria.",institutionString:"Bayero University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:{id:"252115",title:"Mr.",name:"Auwal",middleName:null,surname:"Abdullahi",slug:"auwal-abdullahi",fullName:"Auwal Abdullahi",profilePictureURL:"https://mts.intechopen.com/storage/users/252115/images/system/252115.jpg",biography:"Auwal Abdullahi is a specialist neurological rehabilitation therapist at Bayero University, Kano, where he teaches and supervises both undergraduate and postgraduate students. He is a Fellow of the London of Academy of Sports and Health Sciences in Clinical Neurology Sciences. His most recent publications are on neurobiology of recovery of motor function and clinical decision making. He enjoys reading, research, teaching, and writing.",institutionString:"Bayero University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bayero University Kano",institutionURL:null,country:{name:"Nigeria"}}},coeditorThree:{id:"100142",title:"Prof.",name:"Amit",middleName:null,surname:"Agrawal",slug:"amit-agrawal",fullName:"Amit Agrawal",profilePictureURL:"https://mts.intechopen.com/storage/users/100142/images/system/100142.jfif",biography:"Dr. Agrawal completed his neurosurgery training at the National Institute of Mental Health and Neurosciences, Bangalore, India, in 2003. He is a self-motivated, enthusiastic, and results-oriented professional with more than eighteen years of experience in research and development, as well as teaching and mentoring in the field of neurosurgery. He is proficient in managing and leading teams for running successful process operations and has experience in developing procedures and service standards of excellence. He has attended and participated in many international and national symposiums and conferences and delivered lectures on vivid topics. Dr. Agrawal has published more than 750 scientific articles in various national and international journals. His expertise is in identifying training needs, designing training modules, and executing the same while working with limited resources. He has excellent communication, presentation, and interpersonal skills with proven abilities in teaching and training various academic and professional courses. Presently, he is working at the All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.",institutionString:"All India Institute of Medical Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"8",institution:{name:"All India Institute of Medical Sciences",institutionURL:null,country:{name:"India"}}},coeditorFour:null,coeditorFive:null,topics:[{id:"1056",title:"Neurology",slug:"neurology"}],chapters:[{id:"69646",title:"Aging, Cerebrovascular Burden, and Cognitive Decline",doi:"10.5772/intechopen.89854",slug:"aging-cerebrovascular-burden-and-cognitive-decline",totalDownloads:798,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Brain function is supported by the cerebrovascular system, and changes in vascular phenotype and function through aging process make the brain more susceptible to neurodegenerative diseases, particularly cognitive decline. Correspondingly, the incidence of dementia and the prevalence of neurodegenerative diseases have also increased. In aging, the vessels have been exposed to the inflammatory state by harmful factors referred to as the senescence-associated secretory phenotype (SASP). Aging is a complex process that is associated with accumulated cellular stresses and an increased stress response. The aging in the brain includes structural and functional changes, which cause brain pathologies in the elderly. Particularly, damaged neurovascular event can be a consequent trigger in the pathology of vascular cognitive impairment. This chapter introduces the current knowledge on cognitive decline according to cerebrovascular aging relevant to endothelial senescence and the changes in the SASPs.",signatures:"Kyoungjoo Cho",downloadPdfUrl:"/chapter/pdf-download/69646",previewPdfUrl:"/chapter/pdf-preview/69646",authors:[{id:"176556",title:"Ph.D.",name:"Kyoungjoo",surname:"Cho",slug:"kyoungjoo-cho",fullName:"Kyoungjoo Cho"}],corrections:null},{id:"68688",title:"Hemodynamics in Ruptured Intracranial Aneurysms",doi:"10.5772/intechopen.88695",slug:"hemodynamics-in-ruptured-intracranial-aneurysms",totalDownloads:746,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Incidental detection of unruptured intracranial aneurysms (UIA) has increased in the recent years. There is a need in the clinical community to identify those that are prone to rupture and would require preventive treatment. Hemodynamics in cerebral blood vessels plays a key role in the lifetime cycle of intracranial aneurysms (IA). Understanding their initiation, growth, and rupture or stabilization may identify those hemodynamic features that lead to aneurysm instability and rupture. Modeling hemodynamics using computational fluid dynamics (CFD) could aid in understanding the processes in the development of IA. The neurosurgical approach during operation of IA allows direct visualization of the aneurysm sac and its sampling in many cases. Detailed analysis of the quality of the aneurysm wall under the microscope, together with histological assessment of the aneurysm wall and CFD modeling, can help in building complex knowledge on the relationship between the biology of the wall and hemodynamics. Detailed CFD analysis of the rupture point can further strengthen the association between hemodynamics and rupture. In this chapter we summarize current knowledge on CFD and intracranial aneurysms.",signatures:"Hejčl Aleš, Stratilová Mária, Švihlová Helena, Alena Sejkorová, Radovnický Tomáš, Hron Jaroslav, Feletti Alberto, Koblížek Miroslav, Zámečník Josef, Beneš Vladimír, Dragomir-Daescu Dan and Sameš Martin",downloadPdfUrl:"/chapter/pdf-download/68688",previewPdfUrl:"/chapter/pdf-preview/68688",authors:[{id:"275288",title:"Dr.",name:"Helena",surname:"Švihlová",slug:"helena-svihlova",fullName:"Helena Švihlová"},{id:"297180",title:"Dr.",name:"Aleš",surname:"Hejčl",slug:"ales-hejcl",fullName:"Aleš Hejčl"},{id:"298947",title:"Dr.",name:"Alena",surname:"Sejkorová",slug:"alena-sejkorova",fullName:"Alena Sejkorová"},{id:"298948",title:"Prof.",name:"Martin",surname:"Sames",slug:"martin-sames",fullName:"Martin Sames"},{id:"298950",title:"Dr.",name:"Mária",surname:"Stratilová",slug:"maria-stratilova",fullName:"Mária Stratilová"},{id:"298951",title:"Prof.",name:"Josef",surname:"Zámečník",slug:"josef-zamecnik",fullName:"Josef Zámečník"},{id:"298956",title:"Dr.",name:"Jaroslav",surname:"Hron",slug:"jaroslav-hron",fullName:"Jaroslav Hron"},{id:"306277",title:"Dr.",name:"Tomáš",surname:"Radovnický",slug:"tomas-radovnicky",fullName:"Tomáš Radovnický"},{id:"306278",title:"Dr.",name:"Alberto",surname:"Feletti",slug:"alberto-feletti",fullName:"Alberto Feletti"},{id:"306279",title:"Dr.",name:"Miroslav",surname:"Koblížek",slug:"miroslav-koblizek",fullName:"Miroslav Koblížek"},{id:"306280",title:"Prof.",name:"Vladimír",surname:"Beneš",slug:"vladimir-benes",fullName:"Vladimír Beneš"},{id:"306289",title:"Dr.",name:"Dan",surname:"Dragomir-Daescu",slug:"dan-dragomir-daescu",fullName:"Dan Dragomir-Daescu"}],corrections:null},{id:"68616",title:"Serum Homocysteine and Intracranial Aneurysms",doi:"10.5772/intechopen.88570",slug:"serum-homocysteine-and-intracranial-aneurysms",totalDownloads:547,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Subarachnoid haemorrhage (SAH) occurs as a result of rupture of intracranial aneurysms. SAH causes significant morbidity and mortality. In addition, SAH leads to significant financial burden. In this chapter, we will look into the association between raised serum homocysteine and intracranial aneurysms. In a study on the Han Chinese patients with intracranial aneurysm who were admitted to the hospital, the mean serum total homocysteine level in the patient group with intracranial aneurysm was significantly higher than those in the control group. In the same study, the patients with raised serum homocysteine had 2.196 higher risk of developing intracranial aneurysms. Ren et al. proposed that homocysteine should be seen as an indicator of the risk of intracranial aneurysm and not a direct cause of intracranial aneurysm. In another study, homocysteine increases the development of intracranial aneurysms in rats. Endothelial damage is an early change in the walls of intracranial aneurysms. Polymorphisms of the genes coding for the various components of the vessel walls may be associated with the formation of intracranial aneurysms. In a previous animal study, the size of intracranial aneurysms is significantly smaller in the mice with inducible nitric oxide synthase (iNOS) compared with the mice without iNOS.",signatures:"Mei-Ling Sharon Tai, Tsun Haw Toh, Hafez Hussain and Kuo Ghee Ong",downloadPdfUrl:"/chapter/pdf-download/68616",previewPdfUrl:"/chapter/pdf-preview/68616",authors:[{id:"236979",title:"Dr.",name:"Mei-Ling Sharon",surname:"Tai",slug:"mei-ling-sharon-tai",fullName:"Mei-Ling Sharon Tai"},{id:"303325",title:"Dr.",name:"Kuo Ghee",surname:"Ong",slug:"kuo-ghee-ong",fullName:"Kuo Ghee Ong"},{id:"303326",title:"Dr.",name:"Tsun Haw",surname:"Toh",slug:"tsun-haw-toh",fullName:"Tsun Haw Toh"},{id:"303327",title:"Dr.",name:"Hafez",surname:"Hussain",slug:"hafez-hussain",fullName:"Hafez Hussain"}],corrections:null},{id:"70766",title:"Vascular Calcifications",doi:"10.5772/intechopen.90287",slug:"vascular-calcifications",totalDownloads:536,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Calcium-phosphate levels have an effect on the vascular wall. Calcium is a cation in human body. It is has a crucial effect on intracellular and extracellular mechanisms. Extracellular calcium levels are more than intracellular levels. In total serum, the calcium level is approximately 8.8–10.4. Parathormone and vitamin D regulate blood calcium levels. Phosphorus is more common than calcium in the human body. Most of the phosphorus is present in the skeletal system. Phosphorus level is approximately 2.5–4.5 mg/dl in blood. It is often observed calcification in cardiovascular system in some diseases such as chronic renal failure due to increased calcium-phosphate levels. While the calcification seems in tunica intima layer of the vessel in atherosclerotic disease, it seems in tunica media layer of vessel in chronic renal failure with high uremic level. Vascular calcification is due to arterial stiffness, stenosis, and occlusion. Vascular and valvular calcifications are irreversible. Increased arterial stiffness destroys vascular compliance, causes left ventricular hypertrophy, and disrupts coronary perfusion. As a result, increased vascular calcification is associated with cardiovascular mortality.",signatures:"Mehmet Erin Tüysüz and Mehmet Dedemoğlu",downloadPdfUrl:"/chapter/pdf-download/70766",previewPdfUrl:"/chapter/pdf-preview/70766",authors:[{id:"296173",title:"M.D.",name:"Mehmet Erin",surname:"Tüysüz",slug:"mehmet-erin-tuysuz",fullName:"Mehmet Erin Tüysüz"},{id:"304920",title:"Dr.",name:"Mehmet",surname:"Dedemoğlu",slug:"mehmet-dedemoglu",fullName:"Mehmet Dedemoğlu"}],corrections:null},{id:"71726",title:"Normal Pressure Hydrocephalus",doi:"10.5772/intechopen.92058",slug:"normal-pressure-hydrocephalus",totalDownloads:579,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Normal pressure hydrocephalus (NPH) is characterized by dilated ventricles and a combination of gait impairment, cognition impairment, and loss of urinary control (urgency and incontinence). The only effective treatment for NPH is a CSF shunt; however, only a small percentage of patients ever receive it. The features of gait impairment in patients with NPH are difficult to distinguish from patients of neurodegenerative disorders with motor involvement, such as parkinsonism or dementia with Lewy bodies. CT or MRI imaging is required for the diagnosis of idiopathic normal pressure hydrocephalus. An Evans ratio of more than 0.3 indicates large ventricles, and a ratio of more than 0.33 indicates very large ventricles, but is not specific for idiopathic normal pressure hydrocephalus. The international and Japanese guidelines support shunt surgery as effective treatment of idiopathic normal pressure hydrocephalus, as does the American Academy of Neurology practice guideline. There is a need to provide longitudinal care of patients with idiopathic normal pressure hydrocephalus after shunt surgery as all symptoms respond well to shunt surgery.",signatures:"Ravish Rajiv Keni, Harsh Deora and Amit Agrawal",downloadPdfUrl:"/chapter/pdf-download/71726",previewPdfUrl:"/chapter/pdf-preview/71726",authors:[{id:"100142",title:"Prof.",name:"Amit",surname:"Agrawal",slug:"amit-agrawal",fullName:"Amit Agrawal"},{id:"237362",title:"Dr.",name:"Harsh",surname:"Deora",slug:"harsh-deora",fullName:"Harsh Deora"},{id:"316284",title:"Dr.",name:"Ravish",surname:"Rajiv Keni",slug:"ravish-rajiv-keni",fullName:"Ravish Rajiv Keni"}],corrections:null},{id:"69172",title:"Neuronavigated and Laparoscopic-Assisted Ventriculoperitoneal Shunt Placement",doi:"10.5772/intechopen.89252",slug:"neuronavigated-and-laparoscopic-assisted-ventriculoperitoneal-shunt-placement",totalDownloads:596,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Hydrocephalus is an abnormal accumulation of excess cerebrospinal fluid (CSF) in the brain causing increased intracranial pressure, which can arise from a variety of causes, including congenital, acquired, or idiopathic pathologies. Ventriculoperitoneal (VP) shunting is most commonly used to treat hydrocephalic patients, relieving the increased intracranial pressure by draining excess CSF from the ventricles to the peritoneal cavity. VP shunts are primarily completed using either an open or a more minimally invasive neuronavigated laparoscopic-assisted surgical technique. There is a high level of surgical complications, shunt failures and revision rates following VP shunting. It is suggested that different surgical techniques are associated with varying degrees of patient outcomes, surgical complications, and revision rates, with the less invasive laparoscopic-assisted approach producing improved results. We present our results on 14 consecutive hydrocephalic patients, analyzed retrospectively between 2017 and 2019, investigating the benefits offered by the neuronavigated laparoscopic-assisted insertion of VP shunts. Additionally, we explain our workflow and procedural technique. By investigating these differences, changes can be implemented in current routine procedures to ameliorate patient safety, surgical complications, and revision rates.",signatures:"Sarah Wilson, Michael Crozier and Antonios El Helou",downloadPdfUrl:"/chapter/pdf-download/69172",previewPdfUrl:"/chapter/pdf-preview/69172",authors:[{id:"264606",title:"Dr.",name:"Antonios",surname:"El Helou",slug:"antonios-el-helou",fullName:"Antonios El Helou"},{id:"310388",title:"BSc.",name:"Sarah",surname:"Wilson",slug:"sarah-wilson",fullName:"Sarah Wilson"},{id:"310389",title:"Dr.",name:"Michael",surname:"Crozier",slug:"michael-crozier",fullName:"Michael Crozier"}],corrections:null},{id:"70200",title:"Diagnosis of Symptomatic Intracranial Atherosclerotic Disease",doi:"10.5772/intechopen.90250",slug:"diagnosis-of-symptomatic-intracranial-atherosclerotic-disease",totalDownloads:728,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Intracranial atherosclerotic stroke differs from extracranial atherosclerotic stroke in many aspects, including risk factors and stroke patterns. It occurs in association with in situ thrombotic occlusion, artery-to-artery embolism, branch occlusion, and hemodynamic insufficiency. Intracranial atherosclerotic stenosis (ICAS) could have only been diagnosed by transcranial Doppler (TCD) and transcranial color-coded sonography (TCCS), which are burdened by a risk of bias, or catheter angiography (DSA), which, on the contrary, is very precise, but rarely it is done in clinical practice due to its invasiveness. Computed tomography angiography (CT-A) and magnetic resonance imaging angiography (MR-A) have increased the identification of ICAS in a wider stroke population.",signatures:"Dragoș Cătălin Jianu, Silviana Nina Jianu, Georgiana Munteanu, Traian Flavius Dan and Claudia Birsan",downloadPdfUrl:"/chapter/pdf-download/70200",previewPdfUrl:"/chapter/pdf-preview/70200",authors:[{id:"45925",title:"Prof.",name:"Dragoș",surname:"Cătălin Jianu",slug:"dragos-catalin-jianu",fullName:"Dragoș Cătălin Jianu"},{id:"55071",title:"Dr.",name:"Silviana Nina",surname:"Jianu",slug:"silviana-nina-jianu",fullName:"Silviana Nina Jianu"},{id:"241849",title:"Dr.",name:"Traian Flavius",surname:"Dan",slug:"traian-flavius-dan",fullName:"Traian Flavius Dan"},{id:"241850",title:"Dr.",name:"Claudia",surname:"Birsan",slug:"claudia-birsan",fullName:"Claudia Birsan"},{id:"241852",title:"Dr.",name:"Georgiana",surname:"Munteanu",slug:"georgiana-munteanu",fullName:"Georgiana Munteanu"}],corrections:null},{id:"69829",title:"Poor-Grade Aneurysmal Subarachnoid Hemorrhage: Diagnosis, Therapeutical Management, and Prognosis",doi:"10.5772/intechopen.89993",slug:"poor-grade-aneurysmal-subarachnoid-hemorrhage-diagnosis-therapeutical-management-and-prognosis",totalDownloads:591,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological condition and these patients often have unfavorable outcomes at the long-term follow-up. Poor-grade aSAH is a severe subtype of aSAH and is defined as World Federation of Neurosurgical Surgeon (WFNS) grade IV or V. All patients should be treated by a multidisciplinary team that consists of vascular neurosurgeons, interventional neuroradiologists, neurologists, and anesthetists. Aneurysm rebleeding occurs in the poor-grade aSAH within the first 72 h after ictus. Timing of treatment for aSAH has shifted from delayed to early treatment of ruptured aneurysms, and there will be a trend toward early or ultra-early treatment for poor-grade aSAH. However, there is no consensus regarding the optimal timing of treatment for poor-grade aSAH. Endovascular coiling has provided a viable alternative to surgical clipping. An increasing number of patients have received endovascular treatment. There are limited data on high-level clinical trials focused on the treatment of poor-grade aSAH. An accurate prediction model remains challenging. Predicting long-term outcome is essential to support treatment decision-making. We reviewed the current therapeutical management and prognosis of poor-grade aSAH.",signatures:"Bing Zhao, Haixia Xing, Shenghao Ding, Yaohua Pan and Jieqing Wan",downloadPdfUrl:"/chapter/pdf-download/69829",previewPdfUrl:"/chapter/pdf-preview/69829",authors:[{id:"293852",title:"M.D.",name:"Bing",surname:"Zhao",slug:"bing-zhao",fullName:"Bing Zhao"},{id:"304033",title:"Dr.",name:"Haixia",surname:"Xing",slug:"haixia-xing",fullName:"Haixia Xing"},{id:"304034",title:"Dr.",name:"Shenghao",surname:"Ding",slug:"shenghao-ding",fullName:"Shenghao Ding"},{id:"304035",title:"Dr.",name:"Yaohua",surname:"Pan",slug:"yaohua-pan",fullName:"Yaohua Pan"},{id:"304036",title:"Dr.",name:"Jieqing",surname:"Wan",slug:"jieqing-wan",fullName:"Jieqing Wan"}],corrections:null},{id:"70408",title:"Contrast-Induced Nephropathy",doi:"10.5772/intechopen.90457",slug:"contrast-induced-nephropathy-1",totalDownloads:764,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"With the worldwide increase in the incidence of atherosclerotic coronary artery disease, the rate of coronary interventions has increased. One of the serious complications of this procedure is contrast-induced nephropathy (CIN). This complication can lead to poor outcomes, with an increase in morbidity and mortality of patients. The pathophysiology and risk factors for the occurrence of contrast-induced nephropathy are several and interconnected. The most proposed management of this entity is prophylaxis and thus avoidance of its occurrence. We will take a deeper look on the pathophysiology, the mechanisms by which this complication is aggravated, and how to expect and manage such a problem.",signatures:"Ahmed Shawky Elserafy and Tarek Abdelsalam",downloadPdfUrl:"/chapter/pdf-download/70408",previewPdfUrl:"/chapter/pdf-preview/70408",authors:[{id:"311941",title:"Prof.",name:"Ahmed",surname:"Shawky Elserafy",slug:"ahmed-shawky-elserafy",fullName:"Ahmed Shawky Elserafy"},{id:"312821",title:"MSc.",name:"Tarek",surname:"Abdelsalam",slug:"tarek-abdelsalam",fullName:"Tarek Abdelsalam"}],corrections:null},{id:"68987",title:"Preventing Rupture: Clipping of Unruptured Intracranial Aneurysms",doi:"10.5772/intechopen.88038",slug:"preventing-rupture-clipping-of-unruptured-intracranial-aneurysms",totalDownloads:746,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Unruptured intracranial aneurysms (UIAs) represent a major public health issue due to their unpredictable natural history. Whether to actively treat them or to maintain them under observation remains a hotly disputed topic. In this chapter, we present a review of the literature regarding the history of clipping and its use in UIAs, as well as the experience of our senior author in this field. We performed an extensive Medline and Google Academic search of the relevant literature. We have also made a retrospective analysis on patients harboring UIAs and multiple intracranial aneurysms (MIAs) clipped by the senior author between 1997 and 2017. About 89 patients had solitary UIAs, alongside 101 with MIAs possessing 257 individual aneurysms in total. All UIA patients were discharged with a favorable neurological outcome and no mortality. Concerning MIAs, the majority of cases had 2 aneurysms, the highest number being 6. And, 61 patients from this group had a favorable outcome. In the hands of experienced vascular neurosurgeons, clipping remains a safe option for both UIAs and MIAs. This procedure offers a long-lasting protection from aneurysmal rupture. In the future, new clip technologies and intraprocedural methods of verifying vessel patency and aneurysmal occlusion may further enhance postoperative results.",signatures:"Ioan Alexandru Florian, Teodora Larisa Timis, Cristina Caterina Aldea and Ioan Stefan Florian",downloadPdfUrl:"/chapter/pdf-download/68987",previewPdfUrl:"/chapter/pdf-preview/68987",authors:[{id:"237145",title:"Prof.",name:"Ioan Stefan",surname:"Florian",slug:"ioan-stefan-florian",fullName:"Ioan Stefan Florian"},{id:"292401",title:"Dr.",name:"Ioan Alexandru",surname:"Florian",slug:"ioan-alexandru-florian",fullName:"Ioan Alexandru Florian"},{id:"301858",title:"Dr.",name:"Teodora Larisa",surname:"Timis",slug:"teodora-larisa-timis",fullName:"Teodora Larisa Timis"},{id:"301859",title:"Dr.",name:"Cristina Caterina",surname:"Aldea",slug:"cristina-caterina-aldea",fullName:"Cristina Caterina Aldea"}],corrections:null},{id:"70054",title:"Endovascular Treatment of Brain Aneurysms",doi:"10.5772/intechopen.88964",slug:"endovascular-treatment-of-brain-aneurysms",totalDownloads:1100,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Topic: Chapter discussing the indications for treatment of brain aneurysms, endovascular techniques, tips and tricks. 1. Pathophysiology of aneurysms: Discuss the formation of aneurysms, current thinking of aneurysm development 2. Prevalence/Incidence of aneurysms: Discussion of current state of aneurysm prevalence and how it differs in different populations 3. Unruptured Aneurysms: Diagnosis, Management and Treatment: Imaging paradigms of brain aneurysms, current thoughts on how to follow aneurysms which are being observed, different treatment options for unruptured aneurysms, including clipping, coiling, stent assisted coiling, flow diverter stent, flow disruptors, including the medical management of stent placement 4. Ruptured Aneurysms: Diagnosis, Management and Treatment: Imaging paradigms of ruptured aneurysms, management options for co-morbidities associated with aneurysm rupture, treatment options including coiling, clipping, flow diverter stents, flow disruptors 5. Complication Avoidance: Tips and tricks to avoid complications in the treatment of brain aneurysms.",signatures:"David Altschul, Tarini Vats and Santiago Unda",downloadPdfUrl:"/chapter/pdf-download/70054",previewPdfUrl:"/chapter/pdf-preview/70054",authors:[{id:"297121",title:"M.D.",name:"David",surname:"Altschul",slug:"david-altschul",fullName:"David Altschul"},{id:"308563",title:"Dr.",name:"Santiago",surname:"Unda",slug:"santiago-unda",fullName:"Santiago Unda"},{id:"308564",title:"Ms.",name:"Tarini",surname:"Vats",slug:"tarini-vats",fullName:"Tarini Vats"}],corrections:null},{id:"71184",title:"Brain Cooling and Cleaning: A New Perspective in Cerebrospinal Fluid (CSF) Dynamics",doi:"10.5772/intechopen.90484",slug:"brain-cooling-and-cleaning-a-new-perspective-in-cerebrospinal-fluid-csf-dynamics",totalDownloads:1077,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"The function of the cerebrospinal fluid (CSF) has long been considered for mechanical protection and recently attributed to the supply of nutrients to the brain. However, we hypothesize that the brain is a water-cooled and water-cleaned system. Recent studies on the glymphatic pathways and the introduction of cisternostomy as a surgical procedure for traumatic brain injury reveal a vast and in-depth functionality of the CSF, which works in synchrony with the cardiopulmonary rhythms to act as a buffer for optimum cerebral function. The nasal sinuses are located around the suprasellar cistern, and the evaporating wet mucosa within them during the breathing contributes to local cooling, whereas the nocturnal activation of AQP4 channels allows CSF-ISF exchange. The resultant “cooling and cleaning” of the brain not only maintains a physiological equilibrium but also opens doors for understanding and treating pathophysiology underlying common degenerative and neuro-inflammatory diseases. This chapter describes the novel theory of brain cooling and cleaning and the clinical and experimental evidence to support this hypothesis.",signatures:"Hira Burhan and Iype Cherian",downloadPdfUrl:"/chapter/pdf-download/71184",previewPdfUrl:"/chapter/pdf-preview/71184",authors:[{id:"252247",title:"Dr.",name:"Iype",surname:"Cherian",slug:"iype-cherian",fullName:"Iype Cherian"},{id:"308205",title:"Dr.",name:"Hira",surname:"Burhan",slug:"hira-burhan",fullName:"Hira Burhan"}],corrections:null},{id:"71126",title:"Calcium Channel Blockers",doi:"10.5772/intechopen.90778",slug:"calcium-channel-blockers",totalDownloads:1490,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and necrosis. Coronary vasospasm can lead to significant cardiac ischemia associated with symptomatic ischemia or cardiac arrhythmia. Cerebral vasospasm is an essential source of morbidity and mortality in subarachnoid hemorrhage patients. It can happen within 3–15 days with a peak incidence at 7 days after aneurysmal subarachnoid hemorrhage (SAH). Calcium channel blockers are widely used in the treatment of hypertension, angina pectoris, cardiac arrhythmias, and other disorders like SAH vasospasm related and Migraine. The specific treatment of cerebral vasospasm helps improving cerebral blood flow to avoid delayed ischemic neurologic deficit by reducing ICP, optimizing the rate of cerebral oxygen demand, and enhancing cerebral blood flow with one of the following approaches: indirect pharmacological protection of brain tissue or direct mechanical dilation of the vasospastic vessel. Nimodipine is the standard of care in aneurysmal SAH patients. Nimodipine 60 mg every 4 hours can be used for all patients with aneurysmal SAH once the diagnosis is made for 21 days.",signatures:"Yaser Alahamd, Hisham Ab Ib Swehli, Alaa Rahhal, Sundus Sardar, Mawahib Ali Mohammed Elhassan, Salma Alsamel and Osama Ali Ibrahim",downloadPdfUrl:"/chapter/pdf-download/71126",previewPdfUrl:"/chapter/pdf-preview/71126",authors:[{id:"248884",title:"Dr.",name:"Yaser",surname:"Alahamd",slug:"yaser-alahamd",fullName:"Yaser Alahamd"},{id:"312749",title:"Dr.",name:"Hisham Ab Ib",surname:"Swehli",slug:"hisham-ab-ib-swehli",fullName:"Hisham Ab Ib Swehli"},{id:"312750",title:"Dr.",name:"Sundus",surname:"Sardar",slug:"sundus-sardar",fullName:"Sundus Sardar"},{id:"312751",title:"Dr.",name:"Alaa",surname:"Rahhal",slug:"alaa-rahhal",fullName:"Alaa Rahhal"},{id:"312752",title:"Dr.",name:"Mawahib Ali Mohammed",surname:"Elhassan",slug:"mawahib-ali-mohammed-elhassan",fullName:"Mawahib Ali Mohammed Elhassan"},{id:"312753",title:"Dr.",name:"Salma",surname:"Alsamel",slug:"salma-alsamel",fullName:"Salma Alsamel"},{id:"312779",title:"Dr.",name:"Osama Ali",surname:"Ibrahim",slug:"osama-ali-ibrahim",fullName:"Osama Ali Ibrahim"}],corrections:null},{id:"68364",title:"Aneurysmal Subarachnoid Hemorrhage and Resolution of Inflammation",doi:"10.5772/intechopen.88297",slug:"aneurysmal-subarachnoid-hemorrhage-and-resolution-of-inflammation",totalDownloads:914,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Aneurysmal subarachnoid hemorrhage (SAH) is a severe life-threatening disease and an important source of neurological disability. Therapeutic interventions over the last few decades have repeatedly failed to improve functional outcome after SAH; however, resolution of inflammation has largely been ignored as a potential therapeutic target. The omega-3 fatty acids (FAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are the precursors of key mediators involved in resolution of inflammation and endogenous neuroprotection. EPA also plays a major role in microvascular function, and DHA accretion in the brain is crucial for normal neuronal function. Although considerable loss of brain DHA has been identified in SAH patients, the pathological significance of this process has also been overlooked. Current Western diets provide insufficient amounts of omega-3 FAs to compensate for the loss of brain DHA following SAH. Here, we review the rationale for future clinical trials of omega-3 FAs in SAH. Furthermore, the potential role of defective resolution of inflammation in the growth and rupture of intracranial aneurysms is inferred from recent findings in atherosclerosis and nutrition. The novel concepts of resolution of inflammation and endogenous neuroprotective signaling may open new avenues for public health interventions and innovative research in intracranial aneurysms and SAH.",signatures:"Geisi Saito and Rodrigo Zapata",downloadPdfUrl:"/chapter/pdf-download/68364",previewPdfUrl:"/chapter/pdf-preview/68364",authors:[{id:"297334",title:"Dr.",name:"Rodrigo",surname:"Zapata",slug:"rodrigo-zapata",fullName:"Rodrigo Zapata"},{id:"297336",title:"Dr.",name:"Geisi",surname:"Saito",slug:"geisi-saito",fullName:"Geisi Saito"}],corrections:null},{id:"68237",title:"Post Stroke Depression",doi:"10.5772/intechopen.86935",slug:"post-stroke-depression",totalDownloads:928,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Depression is the most common neuropsychiatric disorder affecting over one third of all stroke patients. The presence of depression after a stroke greatly affects the ability of patients to participate in rehabilitation and can even affect their long-term mortality. Poststroke depression is a well-documented and studied aspect of stroke management because of the implications it has on morbidity, mortality and recovery. Despite post stroke depression being a well-studied phenomenon, it remains underdiagnosed. The development of poststroke depression is multifactorial and has been evaluated from the cellular, genetic, and environmental perspective. Using numerous studies this chapter will review facets of post stroke depression such as epidemiology, etiology and treatment, while evaluating how this phenomena effects patient recovery and rehabilitation.",signatures:"Rena D. Sukhdeo Singh, Abhi Pandhi and Andrei V. Alexandrov",downloadPdfUrl:"/chapter/pdf-download/68237",previewPdfUrl:"/chapter/pdf-preview/68237",authors:[{id:"295155",title:"Dr.",name:"Abhi",surname:"Pandhi",slug:"abhi-pandhi",fullName:"Abhi Pandhi"},{id:"295553",title:"Dr.",name:"Rena D.",surname:"Sukhdeo Singh",slug:"rena-d.-sukhdeo-singh",fullName:"Rena D. Sukhdeo Singh"},{id:"301873",title:"Dr.",name:"Andrei V.",surname:"Alexandrov",slug:"andrei-v.-alexandrov",fullName:"Andrei V. Alexandrov"}],corrections:null},{id:"71221",title:"Available Therapeutics after a Stroke: Current and Promising Options",doi:"10.5772/intechopen.91282",slug:"available-therapeutics-after-a-stroke-current-and-promising-options",totalDownloads:692,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Morbidity and mortality after a cerebrovascular event have increased during the past few years, even after extensive efforts have been made concerning research in prevention, acute treatment, pharmacotherapy, revascularization, and rehabilitation. The functional deficits that arise from an ischemic event are related to the increasing chronic disability that results from lower mortality rates. More people are becoming chronically disabled; currently, as much as 90% of survivors are affected and face difficulties to continue with daily life activities. In this chapter, we briefly review the pathophysiology of ischemia and immediate clinical attention to the event. We argue about the need to seek new pharmacological and non-pharmacological alternatives and discuss the most representative in the field of neuroprotection and neurorestoration. In addition, we review the most relevant dietetic strategies and physical rehabilitation therapies, all aimed at improving the survivors’ quality of life.",signatures:"María Yolanda Cruz Martínez, Karla Alejandra Cantú Saldaña and José Juan Antonio Ibarra Arias",downloadPdfUrl:"/chapter/pdf-download/71221",previewPdfUrl:"/chapter/pdf-preview/71221",authors:[{id:"72488",title:"Dr.",name:"José Juan Antonio",surname:"Ibarra Arias",slug:"jose-juan-antonio-ibarra-arias",fullName:"José Juan Antonio Ibarra Arias"},{id:"180901",title:"M.Sc.",name:"Karla Alejandra",surname:"Cantú Saldaña",slug:"karla-alejandra-cantu-saldana",fullName:"Karla Alejandra Cantú Saldaña"},{id:"303593",title:"Dr.",name:"María Yolanda",surname:"Cruz Martínez",slug:"maria-yolanda-cruz-martinez",fullName:"María Yolanda Cruz Martínez"}],corrections:null},{id:"70926",title:"Rehabilitation Strategies and Key Related Mechanisms Involved in Stroke Recovery",doi:"10.5772/intechopen.91025",slug:"rehabilitation-strategies-and-key-related-mechanisms-involved-in-stroke-recovery",totalDownloads:693,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Poststroke rehabilitation requires a thorough understanding of the neural mechanisms underlying motor function recovery. This chapter outlines these mechanisms and also discusses the corresponding rehabilitation strategies based on the functional characteristics of the brain. The main topics we discuss are as follows: Although ipsilateral brain region activity is inhibited when using the limbs under normal conditions, it is thought that a decrease in this inhibition and the subsequent increased ipsilateral brain area activity post-injury promote recovery in the damaged contralateral neural network. For optimal poststroke motor function recovery, it is important to normalize the resulting imbalance in brain activity. Therefore, increased corticomotor excitation in the injured hemisphere or decreased excitation in the non-injured hemisphere must be promoted. Rehabilitation strategies include reducing non-paretic limb somatosensory input to decrease excitation in the non-injured hemisphere, increasing paretic limb somatosensory input to increase excitation in the injured hemisphere, increasing excitation in the injured hemisphere through movement training of the paretic hand and anesthesia of the paretic upper arm, increasing excitation in the injured hemisphere, or reducing excitation in the non-injured hemisphere. Considering the functional characteristics of the primary motor area, during the early stages after stroke, it is important to increase the somatosensory input to the paralyzed side and combine mental practices using motor imagery.",signatures:"Hideki Nakano",downloadPdfUrl:"/chapter/pdf-download/70926",previewPdfUrl:"/chapter/pdf-preview/70926",authors:[{id:"306863",title:"Prof.",name:"Hideki",surname:"Nakano",slug:"hideki-nakano",fullName:"Hideki Nakano"}],corrections:null},{id:"69503",title:"Supporting Survivors of Stroke in Low Resource Settings",doi:"10.5772/intechopen.86900",slug:"supporting-survivors-of-stroke-in-low-resource-settings",totalDownloads:789,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Stroke occurs suddenly and has major impact on both the survivor and their caregiver. A third of stroke victims usually die from its direct effects or complications. The survivors usually have functional deficits resulting in the need for caregiver support. The caregivers may have inadequate knowledge of how to care for their affected relatives. The result is high caregiver burden and complications among the survivors. Once a person has stroke, it becomes important that their caregivers and their needs are determined so that they get the necessary support from the health professionals. Education of both the stroke survivors and the caregivers, and follow-up to determine if their needs are being met may be the support required. This is important in low resource settings where the survivors and caregivers may not always afford to go to stroke clinics for support visits and follow-up. Furthermore, stroke will result in reduced quality of life, poor functional outcomes, and poor community reintegration, which are important areas in life. Caregivers who look after the survivor for long periods may suffer burnout and have poor quality of life. Educating both the stroke survivor and their caregiver may result in better quality of life and survival rate.",signatures:"Farayi Kaseke, Tecla Mlambo, Aimee Stewart, Lovemore Gwanzura and James Hakim",downloadPdfUrl:"/chapter/pdf-download/69503",previewPdfUrl:"/chapter/pdf-preview/69503",authors:[{id:"294583",title:"Mrs.",name:"Farayi",surname:"Kaseke",slug:"farayi-kaseke",fullName:"Farayi Kaseke"},{id:"302154",title:"Dr.",name:"Tecla",surname:"Mlambo",slug:"tecla-mlambo",fullName:"Tecla Mlambo"},{id:"305976",title:"Prof.",name:"Aimee",surname:"Stewart",slug:"aimee-stewart",fullName:"Aimee Stewart"},{id:"305977",title:"Prof.",name:"Lovemore",surname:"Gwanzura",slug:"lovemore-gwanzura",fullName:"Lovemore Gwanzura"},{id:"305978",title:"Prof.",name:"James",surname:"Hakim",slug:"james-hakim",fullName:"James Hakim"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited 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Ambrosi",coverURL:"https://cdn.intechopen.com/books/images_new/9625.jpg",editedByType:"Edited by",editors:[{id:"221787",title:"Dr.",name:"Patricia",surname:"Bozzetto Ambrosi",slug:"patricia-bozzetto-ambrosi",fullName:"Patricia Bozzetto Ambrosi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"745",title:"Neurodegenerative Diseases",subtitle:"Processes, Prevention, Protection and Monitoring",isOpenForSubmission:!1,hash:"3d5795dad33257368f0b7848c22d5dd4",slug:"neurodegenerative-diseases-processes-prevention-protection-and-monitoring",bookSignature:"Raymond Chuen-Chung Chang",coverURL:"https://cdn.intechopen.com/books/images_new/745.jpg",editedByType:"Edited by",editors:[{id:"33396",title:"Dr.",name:"Raymond Chuen-Chung",surname:"Chang",slug:"raymond-chuen-chung-chang",fullName:"Raymond Chuen-Chung Chang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3278",title:"Neurodegenerative Diseases",subtitle:null,isOpenForSubmission:!1,hash:"aa717c2801cf98db641d48414cef8ced",slug:"neurodegenerative-diseases",bookSignature:"Uday Kishore",coverURL:"https://cdn.intechopen.com/books/images_new/3278.jpg",editedByType:"Edited by",editors:[{id:"155691",title:"Dr.",name:"Uday",surname:"Kishore",slug:"uday-kishore",fullName:"Uday Kishore"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"434",title:"Alzheimer's Disease Pathogenesis",subtitle:"Core Concepts, Shifting Paradigms and Therapeutic 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Zerr"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3437",title:"Mood Disorders",subtitle:null,isOpenForSubmission:!1,hash:"62c54b70da87ce48e712c07601105311",slug:"mood-disorders",bookSignature:"Nese Kocabasoglu",coverURL:"https://cdn.intechopen.com/books/images_new/3437.jpg",editedByType:"Edited by",editors:[{id:"91417",title:"Prof.",name:"Nese",surname:"Kocabasoglu",slug:"nese-kocabasoglu",fullName:"Nese Kocabasoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"628",title:"Clinical and Genetic Aspects of Epilepsy",subtitle:null,isOpenForSubmission:!1,hash:"7a566ad3987bbfe969872a2b89c43559",slug:"clinical-and-genetic-aspects-of-epilepsy",bookSignature:"Zaid Afawi",coverURL:"https://cdn.intechopen.com/books/images_new/628.jpg",editedByType:"Edited 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Henneman",dateSubmitted:"August 18th 2021",dateReviewed:"September 14th 2021",datePrePublished:"October 21st 2021",datePublished:"May 18th 2022",book:{id:"11006",title:"Disinfection of Viruses",subtitle:null,fullTitle:"Disinfection of Viruses",slug:"disinfection-of-viruses",publishedDate:"May 18th 2022",bookSignature:"Raymond W. Nims and M. Khalid Ijaz",coverURL:"https://cdn.intechopen.com/books/images_new/11006.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"104702",title:"Dr.",name:"Raymond W.",middleName:null,surname:"Nims",slug:"raymond-w.-nims",fullName:"Raymond W. Nims"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"414666",title:"M.Sc.",name:"Chris",middleName:null,surname:"Lee",fullName:"Chris Lee",slug:"chris-lee",email:"chris96lee@gmail.com",position:null,institution:null},{id:"415444",title:"MSc.",name:"John R.",middleName:null,surname:"Henneman",fullName:"John R. 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\r\n\tAt present days the expeditious growth of technology and the global population leads to the intemperance of natural gas and fossil fuels. The adequate solution to this issue is energy conversion. Renewable energy resources such as hydropower, wind, tribo, geothermal are most sustainable. In most cases, the wasted energy in day-to-day living is effectively converted into a consumable form of energy. For example, scavenging electrical energy from small-scale physical change with the help of a triboelectric nanogenerator. A greater number of techniques facilitate energy conversion in both the macro and nano units. Hydroelectric, geothermal, electrochemical conversion is widely used energy conversion methods. Meanwhile piezoelectric, triboelectric are blooming techniques in nano energy conversion. This book will intend to provide an overview of existing energy conversion techniques and prominently focus on the development of nano energy conversion to overcome small-scale energy exhaustion. Also features the importance of energy conversion and energy storage systems
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Dr. Chandrasekhar also received the prestigious Brain Korea 21+ Business Research Award from the Ministry of Education for excellence in research work. 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On the other hand, vehicle manufacturers are increasingly facing demands for reducing emissions of harmful gases by the vehicles in accordance with the increasingly stringent legislation.
\nBusses as means of public transportation could reduce considerably the problems caused by the traffic in the urban areas through the usage, among other things, innovative techniques and technologies of vehicle propulsion systems.
\nThe development of innovative technologies is increasingly oriented towards electrification of vehicle propulsion systems expected to lead to: a reduction of harmful emissions, an increased efficiency of vehicles, improved performances, a reduction of fuel consumption, a reduction of noise, and potentially lower maintenance costs. An electric drive technology implies a technology employing at least one drive device called electric motor. Three key electric drive technologies are: hybrid electric, battery electric, and fuel cell electric technologies.
\nIn this chapter the application of electric technologies in the bus propulsion systems is considered through: an analysis of the state of development of city busses, an analysis of the advantages and shortcomings of electric drive technologies, and identification of the problems standing in the way of their greater commercialization. The presented examples of the developed city busses describe the basic characteristics of the applied propulsion systems and their advantages. The development of hybrid technologies for bus propulsion has grown considerably over the past several years. These technologies have reached massive applications in North America and their expansion to Europe has been initiated during the past several years.
\nIn the part of the chapter dealing with hybrid electric busses a typical bus driving system and its components are reviewed and hybrid systems of the major world manufacturers are presented. Special attention is paid to the comparative analysis the hybrid electric busses and conventional and CNG busses. The available literature data have been critically processed and re-presented. Finally, the characteristics of hybrid city busses of some American and European manufacturers which have found the most widespread applications are reviewed.
\nThe fuel cell powered busses draw special attention of users owing the efficiency of their propulsion system and their ability to cut drastically harmful emissions. Even though they are still not widely used, judging by the number of demonstrated projects the development of fuel cell busses is very intensive throughout the world. Barriers to their wider use are very high costs, lack of an adequate infrastructure, and relatively small radius of movement.
\nFuel cell busses are vehicles with zero emissions. CO2 emissions depend on the type and method of production of fuel for fuel cells. In the part of the chapter dealing with fuel cell busses the typical bus configuration, its subsystems, its ecological characteristics, and costs are reviewed. Some of the development projects and characteristics of a new generation of fuel cell busses are presented.
\nBattery electric technologies are among technologies which reduce drastically the impact of a vehicle on the environment, however, they are still far from the proven technologies. The reason is the current level of developing technology of the energy storage devices for these vehicles. Influence of the batteries on commercialization of these busses is more pronounced compared to the other electric drive busses. A significant advancement in the area of energy sources has been made over the past several years by the development of lithium-ion batteries which lead to the development of an increased number of prototypes, even to a series production of these vehicles. In the part of the chapter dealing with battery electric busses the characteristics of some of these realized busses are reviewed.
\nIn a separate part of this chapter the characteristics of energy storage device for the electric propulsion systems of the realized busses are presented, and the expectations from further development trends of the energy source devices are outlined.
\nDepending on the degree of electrification of propulsion system, \nFigure 1\n, three key electric drive technologies for power the electric vehicles are: hybrid electric, battery electric and fuel cell electric technologies [1].
\nDifferent degrees of electrification of road vehicles.
\n
As can be seen from \nFigure 1\n, source of energy to power the vehicle with hybrid electric technologies are fuels, including alternative, which can be used in IC engines and electricity stored in the batteries or ultra capacitors. The charge energy storage to electricity is performed via IC engine and/or via the regenerative braking.
\nSpecial case of hybrid electric technology is plug-in hybrid electric (PHE) technology. It has a battery that can be charged off board by plugging into the grid and which enables it to travel certain kilometers solely on electricity. Vehicles equipped with this technology are called Plug-in Hybrid Electrics Vehicles (PHEVs).
\n\n
\n
Electric drive technologies also, usually, incorporate other technologies, which reduce energy consumption, for example regenerative braking. That allows the electric motor to re-capture the energy expended during braking that would normally be lost. This improves energy efficiency and reduces wear on the brakes.
\nHybrid electric drive configurations
\n
Series hybrid electric drive system.
Series hybrid electric drive system.
\nPower from the generator is sent to the drive motor and/or energy storage batteries according to their needs. There is no mechanical coupling between the engine and drive wheels, so the engine can run at a constant and efficient rate, even as the vehicle changes speed. The serial hybrid technology is the most common hybrid technology.
\n\n
Parallel hybrid electric drive system.
\nParallel hybrid electric drive system.
A series–parallel design, also known as power-split or dual mode hybrid system, is interesting because with proper control strategy it can be designed to take advantage of both parallel and series types and avoid their drawbacks [5].
\n\n
Battery electric drive system.
Battery electric drive system.
\nThe central motor type is currently more common. However, the requirement to transfer power from the motor to the wheels does involve some losses in efficiency
The hub motor type can avoid many of the transmission losses experienced in the central motor type, but are a less regularly used technology.
\n\n
Fuel cell drive without energy storage device (non-hybrid fuel cell vehicles) and
Fuel cell drive with energy storage device (hybrid fuel cell vehicles), \nFigure 5\n.
Fuel cell drive system with energy storage device.
Fuel cell drive system with energy storage device.
\nFuel cell hybrids operate much like other hybrid electric vehicles but with fuel cells producing electricity that charges the batteries, and a motor that converts electricity from the batteries into mechanical energy that drives the wheels [6].
\nThere are some major advantages of electric drive technologies but there are also some disadvantages. \nTable 1\n summarizes the advantages and disadvantages of a hybrid-electric, plug-in hybrid electric battery and fuel cell drive systems [7]:
\nTechnology | \nAdvantages | \nDisadvantages | \n
---|---|---|
\n | \nLower fuelling costs; Reduced fuel consumption and tailpipe emissions; Recovered energy from regenerative braking | \nHigher initial cost; Complexity of two power trains; Component availability | \n
\n | \nCleaner electric energy thanks advanced technologies or renewable; Reduced fuel consumption and tailpipe emissions; Optimized fuel efficiency and performance; Recovered energy from regenerative braking; Grid connection potential; Pure zero-emission capability | \nHigher initial cost; Complexity of two power trains; Component availability-batteries, powertrains, power electronics; Cost of batteries and battery replacement; Added weight | \n
\n | \nUse of cleaner electric energy; Zero tailpipe emissions; Overnight battery recharging; Recycled energy from regenerative braking; Lower fuel and operational costs; Quiet operation | \nMileage range; Battery technology still to be improved; Possible need for public recharging infrastructure | \n
\n | \nZero tailpipe emissions; Higher energy efficiency than the IC engine; Recovered energy from regenerative braking; Potential of near-zero well-to-wheel emissions when using renewable fuels to produce hydrogen; No dependence on petroleum | \nHigher initial cost; Increased reliability and durability; Hydrogen generation and onboard storage; Availability and affordability of hydrogen refueling; Codes and standards development; Scalability for mass manufacture; | \n
Advantages and disadvantages of electric drive technologies.
At the IAA 1969 in Frankfurt, Daimler presented the first electric test bus–an early example of hybrid drive technology. In 1979, Daimler has launched a five-year model trial with a total of 13 Mercedes-Benz OE 305 electric-diesel hybrid busses in regular service. Since 2008 Orion hybrid busses are in regular service on the roads of major U.S. cities, but from 2009 Mercedes-Benz Citaro BlueTec Hybrid is in daily operation [8].
\nThe first sales of serial hybrid city busses in Japan began 1991, when Hino delivered test busses in eight cities.
\nFrom 1997 until today leaders by the number of hybrid busses in commercial use are the United States and Canada.
\nA hybrid electric bus (HEB) usually combines an internal combustion engine with the battery and an electric motor [9]. The ICE can be fueled by gasoline, diesel, or other (natural gas, biofuel) and work either in series or in parallel with the electric motor. Regenerative braking capability in HEBs minimizes energy losses by recovering some of the kinetic energy used to slow down or stop a vehicle.
\nIn a series hybrid configuration [10], \nFigure 6\n, the ICE drives a generator to feed the electric motor and recharge the battery. Braking energy can be captured and stored in the battery (“regenerative braking”). The engine can be downsized compared to a conventional drive-train with the same performance, meaning lower ICE weight and higher energy efficiency.
\nSeries hybrid propulsion system.
Series hybrid propulsion system.
\nThe electric motor powers the drive system, using either energy stored in batteries, or from the engine, or from both as needed [9]. The engine is more efficient at lower speeds and higher load, so the series hybrid is preferred for slow and start-and-stop city driving.
\nIn a parallel hybrid configuration both the engine and the electric motor are linked to the transmission so that either of them, or both at the same time, may provide the power to turn the wheels [11]. Since the parallel hybrid configuration allows the engine to drive the wheels also through a direct mechanical path, it offers better efficiency than a series hybrid configuration, and a more functional and flexible design.
\nThe principal hybrid-electric bus components include [12]: (a) an Auxiliary Power Unit (APU), (b) a drive motor, (c) a controller and inverter, (d) an energy storage device and (e) other auxiliary systems, such as air conditioning and lighting.
\n\n
\n
Electric drive motors are connected to the vehicle wheels either directly, referred to as wheel motors, or through a transmission and differential assembly. Wheel motors are more efficient both in drive cycle and in the regenerative cycle by eliminating the losses in the mechanical transmission and the differential [12]. However, wheel motors are expensive.
\n\n
\n
The major manufacturers of hybrid systems are shown in \nTable 2\n:
\nManufacturer | \nPropulsion system | \nType | \nCountry | \n
---|---|---|---|
BAE | \nHybriDrive | \nSeries | \nUSA | \n
Allison | \nEp40/Ep50 | \nSeries–parallel | \nUSA | \n
ISE | \nThunderVolt | \nSeries | \nUSA | \n
Siemens | \nELFA | \nSeries | \nGermany | \n
Eaton | \nEHPS | \nParallel | \nUSA | \n
Volvo | \nI-SAM | \nParallel | \nCanada | \n
Voith | \nDIWAhybrid | \nParallel | \nGermany | \n
Major manufacturers of hybrid systems.
\n
\n
There are more than 4,600 busses with the Allison Two Mode Parallel Hybrid Systems in operation across 216 cities and 9 countries [14]. The busses have driven more than 600 million kilometers, saved over 75 million liters of fuel and eliminated more than 197.000 metric tones of CO2 [15].
\n\n
ISE components for electric and hybrid drive are manufactured by Siemens (ELFA). ThunderVolt packs have been integrated in over 300 in-service busses, and operated for over 10 million miles (16,09 million km) cumulative [9].
\n\n
Rugged liquid-cooled induction motors with power ratings from 50 kW to 180 kW with reduction gearboxes are used as standard for ELFA traction systems [19]. Permanent-magnet generators are used for all of the latest ELFA traction drive generation. The traction converters play a key role in ELFA traction systems. The complete ELFA traction system is controlled using just one standard traction converter software.
\n\n
An electric motor/generator is located between the output of an automatic clutch and the input to an automated mechanical transmission [22]. The electric motor’s peak output is 44 kW.
\n\n
\n
An advantage of a hybrid-electric bus over a conventional bus is theoretically better fuel economy and lower exhaust emissions [26].
\n\n
Fuel and maintenance (operating) cost savings over the life of the bus are expected to help recover the higher initial (capital) cost. Specifically, operating cost savings are expected through the following features [29]: increased fuel economy; extended brake life; no transmission to service; less moving parts; less engine wear and less expensive engine.
\n\n
There are four primary sources of efficiency and emissions reduction found in HEBs [31]: smaller engine size, regenerative braking, power-on-demand, and constant engine speeds and power output [32].
\nBy adding an electric motor a hybrid electric bus can be equipped with a smaller, more efficient combustion engine.
\nRegenerative braking recovers energy normally lost as heat during braking, and stores it in the batteries for later use by the electric motor.
\nAnother feature that saves energy and reduces emissions in HEBs is the ability to temporarily shut off the combustion engine during idle or coasting modes.
\nIn a hybrid application, the bus can be designed to use its diesel engine only at the engine’s optimum power output and engine speed range.
\n\n
An overall comparison of busses with different technologies (diesel, CNG and hybrid electric) have been realized in the COMPRO project and the results are presented in the report “Cost/effectiveness analysis of the selected technologies” [33]. A comparison of busses is based on several parameters, technological, financial, environmental and planning-based, such as reliability, eployment flexibility, fuel price, range, exhaust gas emissions, noise, extra infrastructual needs. The considerations made above are summarized in \nTable 3\n.
\nDiesel Bus | \nCNG Bus | \nHybrid Electric Bus | \n
---|---|---|
\n
| \n\n
| \n\n
| \n
The comparison between the different technologies of city busses.
Advantages of each compared technology are featured in green, disadvantages in red.
\nAnother comparison is based on a West Virginia University’s (WVU) study of city bus life cycle cost (LCC) [34, 35]. It covers the folowing bus types: diesel busses using ultra low sulfur diesel (ULSD), compressed natural gas (CNG) busses, and hybrid electric busses. LCC factors included capital costs (bus procurement, infrastructure, and emissions equipment) and operation costs (fuel, propulsion-related system maintenance, facility maintenance, and battery replacement) available from the literature.
\nA bus 12-year life cycle cost (LCC) analysis for a fleet of size of 100 busses was performed based on information available in the literature, manufacturers’ specifications, and fuel economy data gathered by WVU [14, 15]. Only technology-dependent factors relevant to bus propulsion were considered; driver and management cost were excluded. Busses were assumed to operate at a national average speed of 12.7 mph (20.48 km/h), to travel for 32.007 mile (about 51.500 km) per year, and to seat 40 passengers for the purposes of calculation.
\nCapital costs for vehicle procurement includes refueling station (CNG bus), depot modification, and emissions reduction equipment (diesel bus).
\nInfrastructure costs for CNG bus technology include two costs: for depot modification and for refueling stations. Operational costs include compression electricity (CNG bus), facility maintenance, propulsion-related system maintenance, battery replacement (hybrid bus), and fuel consumption. Warranty was not considered. Fuel costs were calculated from the product of national annual average mileage, estimated fuel economy, and predicted fuel price. All prices were in 2008 dollars and CNG price data were all converted to the base of diesel (energy) equivalent.
\n\n\nFigure 7\n representing total LCC was created for the capital and operation costs (without fuel consumption), and energy cost, per bus per mile.
\nComparison of life cycle cost between the different bus technologies.
Comparison of life cycle cost between the different bus technologies.
\nThe capital cost hybrid busses was slightly higher than CNG and diesel busses. However, operation cost analysis was similar for all bus types. Although hybrid busses offered the best fuel economy, this was offset by the battery replacement cost. Generally, the LCC total cost showed that diesel busses are still the most economic technology.
\nThe West Virginia University’s report [34] presents estimates for 2007 city bus regulated and greenhouse gas emissions. Tailpipe emissions (particulate matter (PM), nitrogen oxides (NOx) and greenhouse gas (CO2)) and fuel economy estimations were based on recent emissions and fuel economy studies, and adjusted with best engineering approach.
\nFor simpler presentation of emissions and fuel economy by the three typical bus fleets (diesel, CNG and hybrid busses), the results given in the WVU study are appropriately processed and presented in \nFigure 8\n [36]. Comparative values in \nFigure 8\n represent average values for three typical driving cycles (MAN, OCTA, and CBD cycles). As can be seen from \nFigure 8\n hybrid busses were attractive in offering emissions advantages. The estimation showed that hybrid busses offered lower tailpipe CO2, NOx and PM than the diesel and CNG busses. \nFigure 8\n shows that the diesel hybrid bus fuel economy is better than the diesel bus fuel economy about 19%.
\nComparison between the different bus technologies.
Comparison between the different bus technologies.
\nThe use of hybrid technology has become a popular issue in recent years. Hybrid solutions are principally available for all main propulsion types, thus with Diesel, CNG, fuel cells etc. [37]. \nTable 4\n [38, 39] and \nTable 5\n\n\x3c!-- Please check edits, formatting, layout and header row of the Tables 5 and 9 are okay.
Hybrid electric busses manufactured in North America.
Hybrid electric bussses manufactured in Europe.
Besides the mentioned, other manufacturers of hybrid busses are: Gillig, ISE Corporation (North America); Scania, Irisbus Iveco, Van Hool, VDL Bus & Coach, Hess AG (Europe); Tata Motors, Toyota-Hino, Hyundai Motor Company, Mitsubishi Fuso (Asia).
\nFuel cells for bus applications have generated an enormous amount of attention over the last several years, as they offer the promise of a clean, efficient transportation system no longer dependent on fossil fuels.
\nThe fuel cell has a life expectancy about one-half that of an internal combustion engine. Thus, consumers would have to replace the fuel cell twice in order to achieve a vehicle operating lifetime equivalent to that of a traditional engine [41].
\nFuel cell busses (FCBs) require a substantial new infrastructure, support, and training requirements will depend on what type of fuel is used for the fuel cells. Most demonstrations and available busses use pure hydrogen stored in compressed gas form [42].
\nAll fuel cell vehicle concepts use electric motors to power the wheels, typically accomplished through the combination of an electric battery storage system and an on-board hydrogen fuel cell. Depending on the degree of hybridization, the battery may provide pure “plug-in” electricity to drive the vehicle some distance. The battery system would be complemented by a hydrogen storage system and a fuel cell, with the goal of extending the driving range to 300 miles (483 km) [43].
\nEarly fuel cell bus designs involved an electric drive train, where a fuel cell generates electricity which is directly supplied to an electric motor [44].
\nA new generation of FCBs is based on the hybrid concept. \nFigure 9\n shows typical arrangement of the components in FCB [45]. Key system components are: fuel cell system, energy storage system, hydrogen storage system, wheel drive, cooling system, and auxiliaries.
\n\x3c!--Key components of the fuel cell hybrid bus.
\nKey components of the fuel cell hybrid bus.
\n
In a fuel cell vehicle, an electric drive system, which consists of a traction inverter, electric motor and transaxle, converts the electricity generated by the fuel cell system to traction power to move a bus [47].
\nThe fuel cell system and additional aggregates are usually located on top of the roof of the bus.
\nFuel cells are classified by their electrolyte and operational characteristics. For application in vehicles mostly used are the Polymer Electrolyte Membrane (PEM) fuel cells. They are lightweight and have a low operating temperature. PEM fuel cells operate on hydrogen and oxygen from air.
\nAlkaline fuel cells (AFCs) are made by one of the most mature fuel cell technologies. AFCs have a combined electricity and heat efficiency of 60 percent efficient [47].
\nA newer cell technology is the Direct Methanol Fuel Cell (DMFC). The DMFC uses pure methanol mixed with steam. Liquid methanol has a higher energy density than hydrogen, and the existing infrastructure for transport and supply can be utilized [48].
\nThere are some major fuel cell manufacturers supplying fuel cell power plants for heavy-duty applications: Ballard Power Systems and Hydrogenics (Canada), United Technologies Corporation (UTC) Fuel Cells, Enova Systems (USA), Shanghai Shen-Li High Tech Co. Ltd. (China), Siemens and Proton Motor Fuel Cell GmbH, (Germany), Toyota (Japan), Hyundai Motor Co. (South Korea).
\n\n
Lithium-ion battery technology is the most appropriate of energy storage technology for use in the busses. The batteries are usually located on top of the roof of the bus. FCBs are equipped with regenerative braking.
\n\n
The cylinders to storage hydrogen on board operate at an increased pressure of 350 bars.
\n\n
The bus may be equipped with a central traction system which will be located at the left hand side in the rear of the bus. The rear axle has 2 wheel hub motors and has been specifically developed to match the required speeds, load capabilities and energy efficiency. It also serves as a generator for energy regeneration during braking [50].
\n\n
The majority of the stack manufacturers use liquid cooled systems, with radiators to dissipate heat.
\n\n
This will result in a higher efficiency and lower maintenance of the components.
\nFuel cells offer a number of potential benefits that make them appealing for transport use such as greater efficiency, quiet and smooth operation, and, if pure hydrogen is used on board the bus, zero emissions in operation and extended brake life [52].
\nInfrastructure, busses, fuel, and maintenance costs associated with hydrogen fuel cells are currently prohibitively expensive. The cost of facilities has ranged from several hundred thousand dollars up to $4,4 million for a maintenance facility, fueling station, and bus wash [53].
\nCurrently, fuel cells for busses are not a commercial product. The existing fuel cell busses are prototypes, manufactured in fairly small numbers. Fuel cell busses can cost $1 to $3 million (or more) since they are hand-built prototypes utilizing a pre-commercial technology [54].
\nThe hydrogen fuel itself is also currently very expensive. Costs range depending on the method of hydrogen production.
\nOne of the major constraints for use of the fuel cell busses is the refueling time for hydrogen busses.
\nFilling over 30 kg of hydrogen in less than 5 minutes is not currently feasible without pre-cooling the hydrogen (as the temperature increase at these high fill rates would damage the hydrogen tanks) [55].
\nSome comparisons with different bus technologies (Diesel, hybrid diesel-hybrid and fuel cell), in terms of CO2 emissions per km traveled, have shown significant benefits of FCBs [55]. CO2 emissions of fuel cell busses ranging from 0 to 1,8 kg/km. Zero emissions are related to renewable hydrogen and electricity. Emissions of diesel hybrid busses are 0,69 to 1,2 kg/km, but emission of diesel busses are 1,05 to 1,5 kg/km.
\nThe introduction of new types of busses in urban public transport is sometimes a challenging process that includes testing, demonstration and limited production with a tendency to increase the number of vehicles. Fuel cell-powered busses continue to be demonstrated in public transport service at various locations around the world. Many demonstration projects have been launched in the last 10 years in various stages of implementation. Many have been completed, and some of them are still active. An overview of mainly fuel cell city bus development projects is given below [45]:
\n\n
\n
\n
It is funded by the government of Western Australia with support from the Australian government. The project started at mid-2004 and now the busses are decommissioned.
\n\n
\n
The National Renewable Energy Laboratory (NREL) has recently published a status report documenting progress and accomplishments from demonstrations of fuel cell city busses in the United States. The report describes the status and challenges of fuel cell propulsion for transport and summarizes the introduction of fuel cell city busses in North America.
\nThree major programs are [60]:
\n
\n
\n
\n
\n
Production of the second generation of Mercedes fuel-cell hybrid busses started in November 2010 under the CHIC project. Compared with the fuel cell busses which were tested in Hamburg in 2003, the new Citaro FuelCELL Hybrid, \nFigure 10\n, provides several significant new features [61]: hybridization with energy recovery and storage in lithium-ion batteries, powerful electric motors with 120 kW of continuous output in the wheel hubs, electrified power take-off units and further enhanced fuel cells. These should achieve an extended service life of at least six years or 12.000 operating hours [63].
\n\x3c!--The new Citaro FuelCELL hybrid bus.
\nThe new Citaro FuelCELL hybrid bus.
New additions are the lithium-ion batteries which for example store recovered energy. With the power stored there the new Citaro FuelCELL Hybrid can drive several kilometers on battery operation alone. In general, the design of the new FuelCELL busses is largely the same as that of the Mercedes-Benz BlueTec Hybrid busses that run in regular service; these busses also get electrical energy from a diesel generator. Thanks to improved fuel cell components and hybridization with lithium-ion batteries the new Citaro FuelCELL Hybrid saves on almost 50% in hydrogen usage compared with the preceding generation [64]. Overall fuel cell system efficiency has also been improved. The fuel cell bus has a range of around 250 kilometers.
\n\n
Within the project ZEBA demonstration includes 12 new generation fuel cell hybrid busses and two new hydrogen fueling stations [65]. The busses are 12 m, low floor busses built by Van Hool with a hybrid electric propulsion system that includes a UTC Power fuel cell power system (120 kW) and an advanced lithium-ion battery (rated energy: 17.4 kWh and rated power: 76 to 125 kW). Eight Dynetek, type 3 cylinders, 350 bars, are mounted on the roof.
\nThe new busses, \nFigure 11\n, feature significant improvements over two previous generations of fuel cell busses that were demonstrated in California, Connecticut, and Belgium. Improvements include a redesigned Van Hool chassis that is lighter in weight, shorter in height, and has a lower center of gravity for improved weight distribution. The bus has a top speed of 55 mph (88 km/h). The bus purchase cost is about $2,5 million.
\nThe new Van Hool fuel cell bus.
The new Van Hool fuel cell bus.
\nMany transport operators continue to aid the FCB industry in developing and optimizing advanced transportation technologies [66]. These in-service demonstration programs are necessary to validate the performance of the current generation of fuel cell systems and to determine issues that require resolution.
\nBy the end of June 2011, nine of the twelve new Van Hool fuel cell busses had been delivered and seven of those were in-service. The busses have accumulated more than 80.000 miles (128.000 km) and a total of 7.653 hours on the fuel cell systems. The results presented here are early/preliminary information from the first five fuel cell busses that have been placed into service at AC Transit [65].
\n\n\nTable 6\n presents the comparative test results for the Fuel cell and Diesel busses during the evaluating period.
\n\n | Fuel Cell | \nDiesel | \n
---|---|---|
Fuel Cost ($/km) | \n0.96 | \n0.42 | \n
Total Maintenance Cost ($/km) | \n0.94 | \n0.41 | \n
\n | \n\n | \n\n | \n
Operating costs of different busses per kilometer.
During 2011, NREL completed data collection and analysis on new generation FCB demonstrations at three transport operators in the United States: SunLine California, CTTRANSIT Connecticut, and AC Transit California [67]. The current-generation FCBs in service at AC Transit, CTTRANSIT, and SunLine were all of the same basic design: Van Hool (12 m) busses with ISE Corp. hybrid-electric drives and UTC Power fuel cell power systems.
\n\n\nTable 7\n shows the fuel economy of the busses at each location. Data are given in miles per diesel gallon equivalent and in km/liter (1mile per Gallon =0.425 km/liter).
\n\n | FC bus | \nDiesel bus | \nCNG bus | \n|||
---|---|---|---|---|---|---|
mile/gallon | \nkm/liter | \nmile/gallon | \nkm/liter | \nmile/gallon | \nkm/liter | \n|
\n | \n6,8 | \n2,9 | \n4,2 | \n1,8 | \n— | \n\n |
\n | \n5,5 | \n2,3 | \n3,7 | \n1,6 | \n— | \n\n |
\n | \n8,0 | \n3,4 | \n— | \n— | \n3,5 | \n1,5 | \n
Fuel economy of the fuel cell busses at different locations.
The FCBs at the three locations showed fuel economy improvement ranging from 48–133% when compared to diesel and CNG baseline busses. This table also illustrates the variability of the results from fleet to fleet. The results are affected by several factors, including duty-cycle characteristics (average number of stops, average speed, and idle time). Average speed for AC Transit −9,8 mph (15,8 km/h); CTTRANSIT −6,5 mph (10,4 km/h), SunLine −13 mph (20,9 km/h) [67].
\nData about NOx and PM emissions (per year) presented by Van Hool in its promotional materials for three different fleets of busses, are shown in \nTable 8\n [68]. The data are calculated for 50.000 km per year, average speed 20 km/h, and power consumption 50 kW/h.
\n\n | NOx (per year) | \nPM (per year) | \n
---|---|---|
\n | \n62,5 tons | \n1,25 tons | \n
\n | \n25 tons | \n0,25 tons | \n
\n | \nzero | \nzero | \n
Comparative characteristics of NOx and PM emissions for different busses.
Equivalent emissions reduction potential of 100 hybrid fuel cell busses gives a CO2 reduction equal to the uptake of 3.100 acres of forest and a NOx reduction equal to 10 km of 4 lanes of cars [68]. The presented results show all the environmental advantages of the busses with fuel cell technologies.
\nElectric vehicles are a promising technology drastically reducing the environmental impact of road transport. At the same time, EVs are still far from proven technology. Reality is such that battery technology is simply not the whole answer. This is because (especially for large busses) batteries do not carry enough energy to power the bus for a full day.
\nAccording to IDTechEx report [69], “Electric Vehicles 2010-2020” it is estimated that worldwide there are about 480.000 electric busses, mostly small ones - with about 135.000 being bought each year as the fleets grow. Although only 12% of these new busses are electric, it is expected that by 2020 investment in the purchase of these busses will be measured in million of dollars.
\nThe main increase in electric busses will be running the free versions to be used without appropriate infrastructure along the route.
\n\n
Proterra’s battery electric bus.
The busses feature Proterra’s revolutionary clean-transport technology, including the Proterra TerraVolt Energy Storage System, which allows a full battery recharge in less than 10 minutes. Additional bus features include [71]:
Flexible ProDrive and vehicle control system that can operate in battery electric mode or with any small APU to extend vehicle range when needed;
Regenerative braking system, allowing the recapture over 90% of the vehicle’s kinetic energy available during braking;
Light-weight composite body resulting in 25% reduction in weight, significantly lower maintenance costs and 40% longer life than traditional diesel busses.
Proterra’s EcoRide BE35 battery powered busses can operate on standard routes for up to three hours—a range of 30–40 miles (48 to 64 km)—and after that, require just 10 minutes of charging to get back on the road [72].
\nThe busses can accommodate as many as 68 passengers and according to Proterra, will provide $300.000 in savings over the course of their lifetime thanks to lower fuel and transportation costs [73].
\n\n
BYD eBUS-12 electric bus.
BYD, manufacturer of the first long-range (>300 km) all-electric bus (eBUS-12), has been selected as the sole eBUS provider for the 2011 International Universiade Games held in Shenzhen, China. At the core of the eBUS technology is BYD’s in-wheel motor drive system and the Iron Phosphate battery technology. The eBUS also integrates BYD solar panels on the bus roof, converting solar energy to electricity which is stored in the batteries and can completely offset the eBUS air-conditioning load (extending the range on sunny days) [74].
\nBYD has signed a Letter of Intent with the city of Frankfurt, Germany to introduce BYD’s all-electric, long-range, eBUS. BYD will supply three all-electric busses eBUS-12, two DC charging stations and technical support in the first quarter of 2012 [75].
\nBYD is set to trial a full-size, all-electric bus in the Danish capital Copenhagen. Two K9 busses will initially be deployed on ordinary passenger routes from the second half of 2012.
\nThe City of Windsor, Ontario has signed a letter of intent to purchase up to 10 BYD fully electric busses for the community’s transport services in 2012. It will become the first City in North America to launch long-range, all-electric busses [76].
\nBYD has delivered over 300 all-electric busses worldwide and claims orders for over 1.300 more in 2012, making it the largest electric bus manufacturer in the world [77].
\n\n
e-Traction specializes in development of TheWheel as a direct-drive in-wheel motor system with integrated power electronics and fluid cooling [79].
\nTheWheel is designed to deliver very high torque at low revolution.
\nSince 2001, e-Traction is continuously developing in-wheel direct-drive motors for applications ranging from 400 Nm to 10.000 Nm per wheel [80].
\nThe vehicles with TheWheel save up to 40% traction energy and are 50% more fuel efficient compared to the standard diesel equipped bus. The e-Buzs is a “battery dominant” hybrid bus.
\nThis means that it has the ability to run on battery only, with the diesel generator turned completely off.
\nThe diesel unit (with diesel generator) can be replaced and, importantly, the bus returned to revenue service in roughly one hour.
\nIn cooperation with e-Traction, Hybricon, a Swedish company converted two Volvo 7700 city busses to fully electric city bus with rapid charge technology. The busses with the name Arctic Whisper, \nFigure 14\n, are from November 2012 in public service in the city of Umeå, Sweden [81]. e-Traction and Hybricon removed the whole diesel driveline and replaced it with two e-Traction SM/500–3 wheel motors mounted on a rear axle construction. A 100 kWh Valence Li-Fe battery pack (for the purposes of the prototype) and pantographs for the charging station form the basic configuration, with a 50 kW diesel generator as the back-up system.
\nArctic whisper plug in hybrid bus.
The Arctic Whisper’s bus is fast charged for 10 minutes at the end of its route to achieve nearly 100% all-electric operation but with the reliability of diesel.
\nWithout fast charging, the Arctic Whisper has an all-electric runtime of about 2–3 hours with the 100 kW batteries before the diesel generator needs to turn on.
\nFuture plans include using different battery chemistries capable of faster charging and higher charging rates of over 200 kW as well as extending this architecture to 18 meter articulated busses.
\n\n
SMG battery electric bus.
The SMG electric busses are a low floor design, 11,00 m in length and can travel as far as 83 km on a single charge. Using high-speed battery chargers they can be fully charged in less than 30 minutes and have a maximum speed of 100 km/h. Four battery charges are being provided. They use high-capacity lithium-ion batteries and regenerative braking. To reduce their weight and help maximize the distance they can travel between charges, these busses make extensive use of carbon composite materials, instead of metal.
\n\n
Optare’s battery-powered Versa.
\n
Tindo solar electric bus.
Some Tindo bus characteristic are: Length–10,42 m, Motor power peak – 160 kW, Motor power nominal - 36 kW, Speed - 76 km/h, Battery content - 261,8 kWh, Fast Charger Booster Power - 70 kW, Fuel costs - 50% lower than for a diesel bus, Range - 200 km between recharges under typical urban conditions.
\n\n
Optare solo EV battery electric bus.
Around 4.000 Optare Solo EV busses in service worldwide produce zero tailpipe emissions. The model demonstrated in Switzerland is based on a standard 27-seat 8,8 metre Solo, but the technology can be used on other models in the Optare range with higher passenger capacities [86]. The Solo EV has been designed to perform exactly like a standard diesel powered bus, except that it is smoother, quieter and cleaner. It is completely traffic compatible, with good acceleration and hill climbing capabilities and a top speed of up to 90 km/h. On a full charge it has a range of around 110–130 kilometers depending on load factors and topography.
\n\n
Solaris Urbino electric bus.
Solaris Urbino electric bus.
\nThe battery capacity gives the Solaris Urbino electric a range of up to 100 km and a maximum speed of 50 km/h. Batteries are charged with a Walter plug-in connection. A full recharge from the 3x400 V, terminal takes as little as four hours. Even with the 1.400 kg traction batteries, the Solaris Urbino electric is only marginally heavier than its conventional counterparts thanks to the innovative lightweight construction employed.
\nEnergy storage systems, usually batteries, are essential for electric drive vehicles. Batteries must have a high energy-storage capacity per unit weight and per unit cost. Because the battery is the most expensive component in most electric drive systems, reducing the cost of the battery is crucial to producing affordable electric drive vehicles.
\nThe electrical energy storage units must be sized so that they store sufficient energy (kWh) and provide adequate peak power (kW) for the vehicle to have a specified acceleration performance and the capability to meet appropriate driving cycles. For those vehicle designs intended to have significant all-electric range, the energy storage unit must store sufficient energy to satisfy the range requirement in real-world driving. In addition, the energy storage unit must meet appropriate cycle and lifetime requirements [88].
\nThese requirements will vary significantly depending on the vehicle type (battery or fuel cell powered or hybrid electric).
\nThere are many energy storage technology and battery chemistry and packaging options for electric drive busses.
\nBased on the presentation of realized solutions of electric drive busses, in the previous items of this chapter, it may be concluded that in the energy storage devices the latest technology batteries and ultra capacitors are applied. Summary of main characteristics of energy storage devices, for each of the presented busses is given in \nTable 9\n.
\nHYBRID ELECTRIC BUSSES | \n||
---|---|---|
BUS | \n\n | \n\n | \n
\n | \n\n Energy content: approx. 0,5 kWh, Max. charging/discharging power: 200 kW, Voltage: 400–750 V | \n\n Energy content:19,4 kWh, Maximum output of 240 kW and, Located on the roof | \n
\n | \n \n | \n\n \n | \n
\n | \n\n Energy content: approx. 4,8 kWh, Weighting approximately 350 kg, Rated at 600 volts, Located on the roof | \n\n Energy available: >400 Wh, 4x125-Volt Maxwell BOOSTCAP® modules, air-cooled, Design life:10–15 years | \n
\n | \n \n | \n\n \n | \n
\n | \n\n Energy content: 0,5 kWh, Maxwell, 5x125V, Weight 410 kg | \n\n Energy content: 32 kWh, Weight 364 kg, 6 year design life, Roof-mounted | \n
\n | \n||
\n | \n \n | \n\n \n | \n
\n | \n\n Energy content: 26 kWh, Energy storage power 250 kW | \nLi-ion Battery Energy content: 17,4 kWh, Rated power: 76 to 125 kW | \n
\n | \n \n | \n\n \n | \n
\n | \n\n Energy content: 47 kWh | \n\n Energy content: 53 kWh | \n
\n | \n||
\n | \n \n | \n\n \n | \n
\n | \n\n Energy content: 80 kWh | \n\n Energy content: 120 kWh, Rated voltage of 600 V | \n
\n | \n \n | \n\n \n | \n
\n | \n\n Energy content: 324 kWh Milage: 300 km on a single charge | \n\n Battery content: 261,8 kWh | \n
Characteristics of energy storage devices of several bus solutions.
As can be seen from \nTable 9\n, Li-ion batteries are prevailing in the realized bus solutions. In the latest bus solutions Zebra battery and Iron Phosphate battery technology are used. It is notable that the energy capacity of energy storage devices BEBs are significantly higher than that of HEBs and FCBs.
\nIn a HEBs with an ICE that recharges the battery (where battery operates in charge sustaining mode), a lighter and smaller battery is employed.
\nA BEBs require a larger and heavier battery pack, to provide both high energy density and high energy storage capacity so as to maximize the range between recharges.
\nIn the PHEBs one can expect smaller, intermediate-sized, battery packs capable of either charge-sustaining operation in the blended mode with an active ICE, or charge-depleting operation.
\nA number of different battery technologies exist at present [89]. The lead acid battery has been used to supply vehicle electricity for a number of decades. With the introduction of the first modern EVs in the 1980s, the need for more powerful batteries arose. Nickel-cadmium batteries were originally used, later replaced in hybrid vehicles by nickel-metal hydride batteries. However, none of these battery technologies provide the energy density required for sufficient driving distance in pure electric mode.
\nRecently, apart from the mentioned, other energy storage devices are in the intensive growth and expansion, such as: Lithium-ion battery (Li-ion), Li-ion polymer battery, Sodium Nickel Chloride battery (NaNiCl), Lithium iron phosphate battery (LiFePO4), Zinc Air battery, and Supercapacitors.
\nBased on available analysis and current battery data, it appears that the current (2010) battery life should exceed seven years and may be around ten years for ‘average’ use [90, 91].
\nThe most promising chemistries appear to involve silicon, sulfur and air (oxygen) and another important development is research into nanotechnologies. These trends have been widely recognized and a recent presentation by Limotive researchers showed the following battery technology roadmap, \nFigure 20\n [87].
\nThe battery technology roadmap.
The battery technology roadmap.
\nSilicon is an attractive anode material for lithium-ion batteries because it has about ten times the amount of energy that a conventional graphite-based anode can contain [93]. It also has a specific energy of 1.550 Wh/kg – about four times the energy of a conventional graphite-based anode. Furthermore, silicon is the second most abundant element on the planet and has a well-developed industrial infrastructure, making it a cheap material to commercialize with a cost comparable to graphite per unit of weight.
\nThe problem with silicon is that it is very brittle and when lithium-ions are transferred during charge and discharge cycles, the volume expands and contracts by 400% which can pulverize the silicon anodes after just the first cycle.
\nThe Li-Ion technology will become more and more the dominant technology for electro mobility. The Li-Ion technology has not yet reached its full potential, further improvements are still possible.
\nFurther developments are needed to improve capacity and lifetime, reduce volume and costs (currently around €250–€500/kWh for NiMH and €700–€1.400/kWh for Li-ion), and to be safe and reliable [92].
\nAlthough few serious technical hurdles remain to prevent the market introduction of electric powered vehicles, battery technology is an integral part of these vehicles that still needs to be significantly improved. Both current and near-term battery technologies still have a number of issues that need to be addressed in order to improve overall vehicle cost and performance. These issues include [93]:
\n
\n
\n
A significant part in the future reduction of consumption of fossil fuels and of the corresponding reduction of emissions of harmful gases will be played by the alternative propulsion systems and alternative fuels. The development of electric drive technologies intended for application in busses is expanding. However, there are many limitations which at this stage slow down these developments. Sustainability of alternative propulsion systems is dependent upon the degree of their technological development and a compromise between the opposed economical, ecological, and social factors [94].
\nA large number of hybrid busses in North America and Japan and their intense development in Europe over the past several years is a confirmation that their number in the near future will be permanently growing. Although the sale of these vehicles is relatively small, the high cost of fossil fuels and the costs of hybrid vehicles becoming more acceptable will accelerate their further development. The hybrid busses are expected to contribute to further reduction of CO2 emissions, even though some manufacturers have reached the level of 30%. Further improvements in that direction will be dependent on the degree of hybridization of the propulsion system and electronic control which should contribute to the optimization of operation of ICE and hybrid system as a whole.
\nThe experiences so far acquired, through the development of fuel cell busses and many demonstration projects around the world, are very positive. Some reports indicate that the performances of fuel cell busses in-service are above expectation. One of the many barriers to their wider use is the uncertainty of hydrogen supplies and high production costs of hydrogen. Other barriers are related to the security aspects of usage of these vehicles. Despite the insufficient performances of batteries, the next generation of fuel cell busses will be based on the hybrid concept and Li-ion batteries. Some predictions tell that fuel cells for busses will be commercially available within the next 10–15 years. At present, the high cost of busses is one of the greatest barriers to their commercialization.
\nSince 2010 increasing the number of battery driven vehicles and busses is evident, thus it can be expected that in the forthcoming times their number will continue increasing. However, barriers to their massive implementation will be the radius of movement, lack of infrastructure for recharging the batteries and, of course, high cost of the batteries and other power equipment (electric motors and control electronics).
\nFurther challenges for electric drive busses will be the development of battery technologies and of other energy sources.
\nEven though a considerable advancement has been made over the past several years by the development of Li-ion batteries, which have achieved energy density of 95–190 Wh/kg, there is still space for further advancements. The only battery chemistries that have a chance of achieving energy densities in the 1,000 Wh/kg range are rechargeable metal-air and other [95].
\nOther non-chemical energy storage devices include super-capacitors that can reach very high specific power levels for a few seconds, but cannot hold a lot of energy.
\nThe current generation of lithium-ion batteries typically uses a carbon-based anode and a metal oxide cathode. Research on next generation lithium batteries will continue the development of electrode and electrolyte materials and chemistries in order to increase the life and energy density of the battery while reducing size and weight. The most promising chemistries appear to involve silicon, sulfur and air (oxygen) and another important development is research into nanotechnologies [90].
\nFinancial support by Ministry of Education and Science Republic of Serbia (Projects TR 35041, TR 35042 and TR 35036) is gratefully acknowledged.
\nAlternating Current
\nAlkaline Fuel Cell
\nAmerican Public Transportation Association
\nAuxiliary Power Unit
\nBattery Electric Bus
\nBattery Electrics Vehicle
\nBuild Your-Dream
\nCalifornia Air Resources Board
\nCentral Business District
\nClean Hydrogen in European Cities
\nCompressed Natural Gas
\nCarbon Monoxide
\nCarbon Dioxide
\nCOMmon PROcurement of collective and public service transport clean vehicles
\nClean Urban Transport for Europe
\nDirect Current
\nDirect Methanol Fuel Cell
\nEcological City TranspOrt System
\nEaton Hybrid Power System
\nElectric Motor/Generator
\nElectric Vehicle
\nFuel Cell Bus
\nFuel Cell Electrics Vehicle
\nFederal Transit Administration
\nHybrid Electric Bus
\nHybrid Electrics Vehicle
\nInternal Combustion Engine
\nIntegrated Starter Alternator Motor
\nLife Cycle Cost
\nLithium Iron Phosphate
\nLithium-ion
\nLiquid Natural Gas
\nManhattan Cycle
\nSodium Nickel Chloride
\nNitrogen Oxides
\nNational Fuel Cell Bus Program
\nNational Renewable Energy Laboratory
\nOrange County Transit Authority
\nPolymer Electrolyte Membrane
\nPlug-in Hybrid Electric Bus
\nPlug-In Hybrid Electrics Vehicle
\nParticulate Matter
\nSeoul Metropolitan Government
\nSustainable Transport energy for Perth
\nUltra Low Sulfur Diesel
\nUnited Technologies Corporation
\nWest Virginia University
\nZero Emission Bay Area
\nPlease note that citations for reference [91] is missing. Please provide the citations or delete the references from the list.
\nProgression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). The activity of CDKs is controlled by their binding to coactivator subunits termed Cyclins, as well as by CDK inhibitory proteins termed CKIs. The accumulation of both Cyclin and CKI proteins is tightly regulated at the level of transcription. In addition, Cyclin and CKI proteins are controlled at the level of their destruction. Remarkably, during each and every passage through the cell cycle, Cyclins, CKIs, and hundreds of other proteins, accumulate and are subsequently destroyed via a highly regulated process of programmed degradation. This degradation is controlled by ubiquitin.
\nUbiquitin is conjugated to substrate lysines, and because ubiquitin itself contains seven lysine residues to which ubiquitin can be added, the repetitive addition of ubiquitin can result in the formation of polyubiquitin chains on substrates. These chains can be formed through each of the different lysines in ubiquitin, as well as through the amino-terminal methionine, leading to chain formations that adopt distinct topological features [1, 2]. The most well-characterized of these are chains linked through lysine 48 in ubiquitin, so-called K48-linked ubiquitin chains, which target substrates to the proteasome for destruction. More recently, K11-linked chains were also shown to target substrates to the proteasome [3, 4]. Alternatively, ubiquitin chains linked through other lysines (or through methionine 1) lead to diverse signaling outputs by altering protein-protein interactions, protein localization, enzyme activity, etc. This already complex picture is further complicated by the recent discovery of branched ubiquitin chains, which contain non-homogeneous lysine linkages. For example, branched K11/K48 chains likely represent remarkably strong degradative signals [5, 6].
\nProtein degradation through the ubiquitin proteasome system (UPS) is the major regulator of programmed protein destruction in human cells and plays an outsized role in controlling cell cycle progression [7]. Importantly, the targeted degradation and/or stabilization of specific proteins at transition points (e.g. mitosis/G1 and G1/S boundaries) promotes cell cycle progression, provides directionality and irreversibility to the cell cycle and maintains genome integrity [8]. Accordingly, numerous enzymes in the ubiquitin system have been implicated in these transition points.
\nThe start of DNA replication represents a tightly controlled barrier to proliferation in normal cells. As such, nearly all of the non-dividing cells in the human body are arrested prior to the start of S-phase, in either G1, or in quiescence (G0), where they maintain the equivalent of G1-phase (2C) DNA content. In diseases of uncontrolled proliferation, and most notably in cancer, the S-phase boundary is perturbed. Thus, cancer cells are able to aberrantly enter S-phase due to a weakening of the G1/S border [9]. The retinoblastoma tumor suppressor pathway plays a key role in controlling G1/S. However, the ubiquitin system is also tightly linked to G1/S regulation in normal and cancer cells. Below, we will discuss the particular enzymes and pathways associated with ubiquitin signaling that have been implicated in regulating the start of S-phase.
\nThe RING domain family of E3 ubiquitin ligases is the largest family of E3s in higher eukaryotes, and in humans it is represented by several hundred unique enzymes and/or enzyme complexes. The cullin RING ligases (CRLs) are the largest subfamily of RING E3s, encoding nearly 300 unique enzymes. The CRL E3s all share a common molecular architecture [10]. CRLs utilize a cullin protein backbone, which simultaneously binds to both an E2 ubiquitin conjugating enzyme and substrate, positioning E2 and substrate in close proximity, and enabling the rapid transfer of ubiquitin onto substrates (Figure 1A).
\nArchitecture of the cullin RING E3 ubiquitin ligases. (A) Architecture of a canonical CRL E3 ligase. (B) Boxes highlighting the substrate targeting (dark blue) and ubiquitin transfer (purple) modules.
The human genome encodes several cullin proteins, including Cul1, Cul2, Cul3, Cul4A, Cul4B, Cul5, Cul7, Cul9 and the related cullin-like protein APC2. With the exception of APC2, each cullin is thought to assemble into a ligase with a similar architecture, where the amino terminus of the cullin engages targets and functions as a substrate targeting module, and the carboxy terminus engages the E2, functioning as a ubiquitin transfer module (Figure 1B). Cullin binding to substrates and E2-ubiquitin conjugating enzymes is indirect. Most cullins first bind to an adaptor protein which in turn binds to a family of substrate receptors that then recruit substrates for ubiquitination (Figure 1). Similarly, cullin proteins indirectly interact with one of two RING domain containing proteins (Roc1/Rbx1 or Roc2/Rbx2) which in turn bind to E2 ubiquitin conjugating enzymes. This architecture is shared among all known CRL complexes.
\nThe archetypical CRL sub-family, and one which will be discussed in greater detail, is the Skp1-Cul1-F-box family of CRLs. These ligases, commonly referred to as SCF or CRL1 ligases, utilize a family of 69 interchangeable substrate receptor proteins, termed F-box proteins, which designate substrates for ubiquitination and degradation. F-box proteins rely on an F-box domain to interact with an adaptor protein termed Skp1, which bridges F-box proteins to Cul1 (Figure 2). The CRL nomenclature dictates that specific ligase complexes are depicted with the F-Box protein as a superscript, following the name of the cullin complex. Thus, Cul1-based CRLs, in complex with the F-box substrate receptor Skp2, are designated as SCFSkp2 or CRL1Skp2 (hereafter, Cul1-based CRL complexes will be referred to as SCF).
\nArchitecture of the SCF ligase. (A) Example of an SCF-type ligase bound to a short linear degron sequence motif in a substrate. (B) Example of an SCF-type ligase bound to phosphorylation-dependent degron in a substrate.
Importantly, substrate receptors recognize proteins for degradation based on short, linear sequence motifs, called degrons. Degron sequences are shared among the substrates of a specific E3. In addition, degrons are transferrable, and the addition of degron sequences to non-substrates is often sufficient to trigger their recognition by the E3 and subsequent ubiquitination and degradation. Also, many substrate receptors, although not all, require post-translation modification (e.g. phosphorylation) of the substrate within the degron for the substrate to be recognized, ubiquitinated, and degraded. Thus, the degradation of many SCF substrates is regulated at the level of the substrate and is a two-step process. First, the substrate must be present and modified, and second, the ligase must also be available, thereby enabling substrate recognition and degradation. It is important to note that each substrate receptor can have many substrates. Furthermore, individual substrates can be controlled by multiple ligases. Finally, distinct substrate adaptors can themselves be targeted for degradation by other E3 ligases.
\nThe Cul1-based SCF ligases are the founding members of the CRL family. They were first discovered in yeast based on their role in controlling cell cycle progression. Their discovery grew out of gain-of-function screens performed by Elledge and colleagues, which identified suppressors of the yeast cell cycle mutant Cdc4. This screen uncovered a new protein, whose mRNA and protein levels oscillated during the cell cycle. Moreover, the amino acid sequence of this new protein included a Cyclin homology domain, similar to that found in the previously identified Cyclins A, B, D, and E. Thus, this new protein was named Cyclin F [11]. Significantly, Cyclin F contained a domain with sequence similarity to Cdc4, which they named the F-box domain. They found that the F-box domains in Cyclin F and Cdc4 were essential for tethering both proteins to the ubiquitin machinery via binding to Skp1 [12]. Shortly thereafter, the Harper lab, in collaboration with Elledge, as well as the Deshaies lab, showed that SCF complexes could trigger the ubiquitination and degradation of the yeast CDK inhibitor Sic1. Moreover, these studies demonstrated that the F-box protein Cdc4 preferentially bound to the phosphorylated version of Sic1, thereby triggering its ubiquitination and degradation [13, 14].
\nLike other E3 ubiquitin ligases, the Anaphase Promoting Complex/Cyclosome (APC/C) plays an important role in protein degradation. APC/C regulates the ubiquitination and degradation of the CDK activator proteins Cyclin A and Cyclin B, in addition to many other cell cycle regulated proteins. As such, it is a core component of the cell cycle oscillator. As its name suggests, the APC/C is activated in metaphase of mitosis, during which time it triggers the ubiquitination and degradation of numerous proteins including two critical substrates, Cyclin B and securin, thereby “promoting anaphase” and mitotic exit. In addition to its essential function in mitosis, APC/C also plays an evolutionarily conserved role in G1-phase. The APC/C remains active throughout G1, where in contrast to its role in promoting progression through mitosis, the APC/C restrains progression through G1-phase into S-phase [17], and is not turned off until immediately prior to the start of DNA replication [15, 16]. Significantly, APC/C inactivation at the G1/S boundary is required for the start of S-phase.
\nSimilar to the CRLs discussed above, the APC/C has both a cullin-like subunit (APC2) and a RING subunit (APC11). However, the APC/C is significantly different than the CRL ligases discussed above. Notably, the APC/C is composed of 18 polypeptide subunits and is a remarkable 1.2 mDa in size (Figure 3). The cullin subunit, APC2, is the most divergent of the cullins, and lacks features that are common among other cullin proteins. For example, while other cullin proteins are post-translationally modified and activated by the small, ubiquitin-like protein Nedd8, this process is not thought to be involved in APC/C activity.
\nArchitecture of the APC/C ubiquitin ligase. The color scheme is the same as above for SCF ligases. Several proteins are specifically shown, including the cullin subunit APC2, the RING subunit APC11, and the substrate receptor Cdh1. Note that there are many more components.
The APC/C utilizes either of two substrate receptors during somatic cell cycles. First, during mitosis, the APC/C binds to the substrate receptor/coactivator Cdc20, which brings Cyclin B and Securin to the APC/C for ubiquitination. Immediately following mitotic exit, APC/C shifts to using a second substrate adaptor, the Cdc20-related protein Cdh1/Fzr1 (hereafter referred to as Cdh1). The Cdh1-bound form of APC/C remains active throughout G1-phase and targets a myriad of cell cycle regulators for degradation, including proteins involved in transcription, nucleotide metabolism, and CDK activation. Thus, it is APC/CCdh1 that must be inactivated prior to the beginning of S-phase. Both Cdc20 and Cdh1 recognize substrates via short, linear degron motifs in substrates. The most well-characterized and widespread of these degron motifs among APC/C substrates are the D-box (amino acid sequence R-X-X-L, where X is any amino acid) and the KEN box (amino acid sequence K-E-N). Thus, the ability of Cdc20 or Cdh1 to recruit substrate proteins harboring D- or KEN-box motifs to the APC/C is required for the subsequent ubiquitination and destruction of APC/C targets.
\nLike the SCF, the APC/C was identified by virtue of its key role in cell cycle. It had been known that the key CDK activator Cyclin B is controlled by degradation, and that both the accumulation and degradation of Cyclin B play a vital role in cell cycles, particularly in early frog embryos [18]. In 1995, the regulator of Cyclin B was discovered by the Kirschner and Hershko labs, who named it the Anaphase Promoting Complex and Cyclosome, respectively [19, 20].
\nThe SCF complexes can assemble from any one of 69 well-established substrate receptor F-box proteins in humans. A subset of SCF ubiquitin ligase complexes have been directly implicated in G1/S control. Here we will discuss the role of each of these distinct complexes and/or substrate receptors, aspects of their regulation and function, and their contribution to G1 progression and S-phase initiation.
\nThe yeast specific Cell Division Control gene/protein 4, called Cdc4, was one of the original cell cycle mutants identified by Hartwell and colleagues, who later received the Nobel Prize for the analysis of cell cycle in budding yeast. They showed that Cdc4 mutant yeast arrest at the G1/S boundary, prior to the start of DNA replication [21]. However, it took another 20 years for the essential molecular function of Cdc4 in promoting cell cycle progression to become clear, and in doing so, laid the foundation for the discovery of CRL ligases.
\nAs the analysis of cell cycle control became increasingly popular in the late 1980s and early 1990s, researchers revisited the role of Cdc4. Nasmyth and colleagues showed that the budding yeast Cdc4 mutants, which arrest before the start of DNA replication when grown at their restrictive temperature, lack appreciable CDK activity [22]. Interestingly, cell cycle arrest is caused by an inability of Cdc4 mutant cells to downregulate the yeast CKI Sic1, which normally decreases at the end of G1. The decrease in Sic1 allows the increase in CDK activity needed to enter S-phase. Thus, yeast cells cannot enter S-phase when Cdc4 is inactivated [11].
\nAs discussed above, Cdc4 is an F-box protein that binds to Sic1, promoting its ubiquitination by the SCFCdc4 complex. The mechanism by which Cdc4 recognizes Sic1 to promote its degradation provides a clear example of the interplay between phosphorylation and ubiquitination cascades. Interestingly, Sic1 must first be phosphorylated by Cyclin-CDK complexes, and this phosphorylation enables the binding of Cdc4 to Sic1 [13, 14]. Once phosphorylated and bound to Cdc4, Sic1 is recruited to the SCF complex for ubiquitination (Figure 4). Thus, CDKs promote their own activity at the G1/S boundary by triggering the degradation of their inhibitor, Sic1 (Figure 4B). This implies a positive feedback loop in control of S-phase entry. While the mechanism by which Cdc4 controls G1/S is largely attributed to its role in destroying Sic1, Cdc4 has also been linked to other cell cycle regulators and proteins involved in proliferative control. Cdc4 substrates include numerous proteins involved in MAPK signaling that mediate cell cycle arrest in response to pheromone [23, 24, 25, 26], the replication regulator Cdc6 [27], the sirtuin deacetylase Hst3 [28], as well as proteins involved in sister chromatid cohesion [29], regulation of calcineurin [30], and mating-type switching [31]. Because Cdc4 has many substrates, it plays a complex and multi-faceted role in yeast cell cycle, among other processes.
\nSCFCdc4 promotes S-phase entry in yeast by triggering the degradation of the CKI Sic1. (A) Binding between Sic1 and Cdc4 is triggered by phosphorylation of Sic1, which then promotes Sic1 ubiquitination and degradation. (B) A positive feedback loop between Cdc4, Sic1 and CDK promotes S-phase entry.
The F-box protein Skp2 has been well-characterized in human cells and plays an important role in the G1/S transition. Similar to Cdc4, Skp2 plays a key role in regulating CDKs by promoting the destruction of CKI proteins. In particular, Skp2 plays an important role in promoting the destruction of the human CKI p27 [32, 33]. Moreover, the ubiquitination of p27 by SCFSkp2 requires that it first be phosphorylated by CDK, and this subsequently targets p27 for destruction, suggesting a similar positive feedback loop in G1/S regulation (Figure 5) [34]. Similarly, SCFSkp2 can target two other CKI proteins for degradation. These are p21 and p57, both of which are degraded in proliferating cells going through the cell cycle [35, 36], although p21 is also degraded by a second Cul4-based CRL ligase once DNA replication has begun [37]. Finally, Skp2 has been linked to the degradation of the retinoblastoma related protein RBL2/p130 [38, 39]. Like RB, RBL2/p130 restrains the activity of a cell cycle E2F transcription factor that promotes proliferation and cell cycle progression.
\nSCFSkp2 promotes S-phase entry in humans by triggering the degradation of the CKI p27. (A) Binding between p27 and Skp2 is triggered by phosphorylation of p27, which then promotes p27 ubiquitination and degradation. (B) A positive feedback loop between Skp2, p27 and CDK promotes S-phase entry.
As might be expected, Due to its role in promoting S-phase via the degradation of CKIs, Skp2 is often overexpressed in cancers, which likely contributes to cancer cell proliferation [40]. Chemical approaches aimed at identifying Skp2 inhibitors have been undertaken, with some success [41, 42].
\nIn addition to its role in regulating several target proteins, including the CKIs discussed above, Skp2 plays a complex and more paradoxical role in regulating proliferation. The Myc transcription factor is a potent oncogene, that is activated in many cancers and which drives proliferation through myriad mechanisms [43]. Myc is ubiquitinated by Skp2 [44, 45]. However, remarkably, the ubiquitination and degradation of Myc catalyzed by SCFSkp2 triggers an
Interestingly, Skp2 is itself regulated by ubiquitin mediated proteolysis. Skp2 is targeted for degradation by the Anaphase Promoting Complex/Cyclosome during G1-phase of the cell cycle [48, 49]. The degradation of p27 requires the upregulation of Skp2. This degradation would presumably occur after Skp2 levels accumulate, following the inactivation of APC/C, which occurs in late G1. That is, APC/C inactivation should lead to an increase in Skp2 levels, since Skp2 would no longer be degraded. Only then could Skp2 promote the degradation of p27. However, this complex order of events remains unclear and has not yet been tested directly. Since the abundance of CKIs, like p27, should prevent the activation of G1/S CDKs, this also implies that APC/C inactivation precedes CDK activation. As discussed below, this too remains unknown, and recent evidence suggests, in fact, that APC/C inactivation occurs after CDK activation in G1 [16].
\nIn addition to its regulation by ubiquitination, Skp2 is also regulated by phosphorylation. This phosphorylation is mediated, in part, by the oncogenic kinase AKT [50]. Notably, AKT kinase activity is cell cycle regulated, and begins to increase in late G1-phase [51]. Skp2 phosphorylation by AKT increases Skp2 stability and alters its localization. Surprisingly, SCFSkp2 also ubiquitinates AKT, and enhances AKT activation [52]. The degradation of p27 and activation of AKT and Myc, by Skp2, are likely to play an important role in tumor biology and treatment. The degradation of p27, a negative cell cycle regulator, creates an environment more permissive to proliferation because cells lacking p27 can progress through the cell cycle more rapidly. In addition, the activation of AKT and Myc could contribute significantly to cancer cell cycles.
\nThe eponymous Cyclin F is the founding member of the F-box family of E3 ubiquitin ligases [11, 12, 53]. Cyclin F is unique among F-box proteins in that it contains a Cyclin homology domain, similar to canonical Cyclins that bind and activate CDKs. However, unlike those other Cyclins, Cyclin F neither binds nor activates a CDK [53]. In addition, Cyclin F levels oscillate strongly throughout the cell cycle, and this is the result of both changes in its transcription and degradation. Notably, Cyclin F is the only F-box protein that was identified as cell cycle regulated in all global studies of human cell cycle transcriptional dynamics [54]. Accordingly, Cyclin F knockout mouse embryonic fibroblasts showed a strong defect in cell cycle entry following synchronization in quiescence [55]. Nevertheless, despite this strong cell cycle phenotype and being the first described F-box protein in higher eukaryotes, Cyclin F went a long time without having a bona fide substrate.
\nThe first two substrates described for Cyclin F were the centrosome protein CP110 and the spindle associated, mitotic phospho-protein NUSAP1 [56, 57], further supporting a role in cell cycle, and pointing to a function in organizing the microtubule cytoskeleton. In addition, Cyclin F regulates the RRM2 subunit of ribonucleotide reductase [58], histone mRNA stem loop binding protein SLBP [59], and the DNA replication protein Cdc6 [60], highlighting a role in S-phase progression and genome stability.
\nImportantly, Cyclin F regulates the degradation of Cdh1, the substrate receptor for the APC/C ubiquitin ligase (Figure 6). APC/CCdh1 is activated throughout G1-phase and its inactivation is critical for S-phase entry. Thus, Cyclin F-mediated degradation of Cdh1 was shown to play a critical role in entry into S-phase [61]. Interestingly, in addition to targeting the APC/C substrate receptor Cdh1 for degradation, Cyclin F is also a substrate of APC/C in mitosis and early G1-phase [61]. Thus, Cyclin F exists in a double-negative feedback loop with APC/C, where it is a substrate in mitosis and early G1, and then the regulator of Cdh1 degradation in late G1 and S-phase (Figure 6).
\nSCFCyclin F and APC/C constitute a double-negative feedback loop. (A) APC/CCdh1 targets Cyclin F for degradation in late mitosis and early G1. (B) SCFCyclin F targets Cdh1 for degradation in late G1 and S-phase. (C) Together, this suggests a temporally ordered, double negative feedback loop that promotes S-phase entry.
Like Skp2, Cyclin F is also phosphorylated by the oncogenic kinase AKT [62]. Similar to Skp2, the phosphorylation of Cyclin F by AKT leads to a significant increase in Cyclin F stability. Phosphorylation by AKT enhances Cyclin F assembly into SCF ligase complexes. Thus, phosphorylation contributes to the switch in Cyclin F, from being an APC/C substrate to being capable of targeting for Cdh1 degradation in late G1-phase [62]. The tight regulation of Cyclin F throughout the cell cycle, its substrates, phosphorylation by AKT, and regulation by other E3s, point to its critical role in cell cycle progression. Moreover, these results suggest that Cyclin F is a key regulatory node mediating the interaction between AKT-dependent growth factor signaling and the core cell cycle machinery.
\nThe SCFFbxw7 ubiquitin ligase (also called SCFFBW7 or SCFFBXO30) is the most tightly linked to cancer proliferation of all SCF-type E3s [63]. Fbxw7, is highly mutated in human cancers, and exhibits both truncating mutations throughout its gene body, as well as “hotspot” point mutations in its substrate binding motif. Interestingly, while Fbxw7 is generally considered a tumor suppressor [64], “hotspot” mutations are more commonly found in oncogenes, such as the common G12V mutation recurrently observed in oncogenic K-Ras in many human malignancies. SCFFbxw7 promotes cell cycle progression by regulating the degradation of Cyclin E, the key activator of CDK2 at the G1/S boundary [63, 65, 66, 67]. In addition, Fbxw7 regulates the ubiquitination and destruction of numerous other pro-proliferative and cancer associated proteins, including Myc [68, 69], Notch [70, 71] and Jun [72].
\nSimilar to other SCF ligases, the SCFFbxw7 ligase recognizes substrates through phospho-degron motifs, with the most well characterized being that on Cyclin E. The phosphorylation of Cyclin E, by CDK2 or GSK3, can promote the degradation of Cyclin E by enhancing its binding to Fbxw7 [64, 66, 67, 73]. In addition, Fbxw7 homo-dimerizes, and this dimerization plays an important role in its ability to target substrates for degradation [74].
\nEmi1 is a cell cycle regulated F-box domain-containing protein. However, Emi1 is unique among F-box proteins in that it has no known substrates, despite the fact that it binds tightly to the SCF adaptor Skp1. Emi1 is instead a key regulator of the cell cycle E3 ligase APC/C [75].
\nMany studies have demonstrated the potent and extensive role that Emi1 plays in inhibiting APC/C. Emi1 acts as a pseudo-substrate for APC/C, blocking the binding and ubiquitination of substrates [76]. In addition, Emi1 can alter the binding of the APC/C E2 ubiquitin conjugating enzymes, providing additional layers of regulation [77, 78, 79].
\nThe association of Emi1 with S-phase entry is complex. Based largely on gain-of-function approaches, Emi1 was shown capable of inhibiting APC/C at the G1/S boundary and promoting S-phase entry [80]. This was fitting, since Emi1 abundance is controlled by the E2F family of transcription factors, which are activated in mid G1 and promote G1/S [80]. However, loss of Rca1, the fly version of Emi1, leads to an accumulation of cells in later stages of the cell cycle, not at G1/S [81]. Similarly, the loss of Emi1 in human cells was reported to induce the reactivation of APC/C during S and G2-phase, and to induce DNA re-replication as a result of the degradation of proteins which normally restrain licensing of replication origins [82, 83]. However, consistent with early gain-of-function studies, recent single cell approaches suggest that Emi1 contributes to the kinetics of APC/C inactivation at G1/S, and that Emi1 locks APC/C in an off state once S-phase begins [16]. Surprisingly, Emi1 might also be a substrate of the APC/C [84]. If Emi1 is a substrate of APC/C, this implies that Emi1 could be ubiquitinated by APC/C in early G1, and that it later accumulates as an inhibitor to inactivate APC/C and promote S-phase entry, much like Cyclin F [84]. This adds to our understanding of Emi1 degradation, wherein previous studies had shown it was degraded in mitosis by the SCFbTRCP ubiquitin ligase [85, 86]. It will be important in the future to determine if altering the ubiquitination and degradation of Emi1 by APC/C accelerates progression through G1/S and to determine how this is coordinated with other SCF ligases that regulate G1/S.
\nAn extensive body of evidence has defined the role of APC/CCdh1 in G1/S control [17]. Early studies in yeast showed that Cyclin proteolysis starts in late mitosis but then persists as cells continue through G1-phase [87]. In addition, yeast cells lacking Cdh1 are defective at arresting in G1-phase. Similar results have been observed across all eukaryotes in which loss of Cdh1 has been studied, including worms [88, 89], flies [90], chickens [91], mice [92] and humans [16, 61, 93]. The loss of Cdh1 accelerates progression through G0/G1 and promotes the start of S-phase. In addition, cells lacking Cdh1 are universally defective in G0/G1 arrest [17]. Accordingly, single allelic loss of Cdh1, the APC/C substrate receptor/coactivator in G0/G1-phase, is sufficient to cause tumors in mice [94]. Since the APC/C controls the stability of many dozens of substrates, it is unlikely that any one provides the basis for how cells enter S-phase in the absence of G1 APC/C function. Instead, it is more likely that the concerted upregulation of many cell cycle drivers together provides an explanation for the vital role of APC/C in restraining G1/S. Nevertheless, the APC/C is among a small group of key signaling molecules that prevent entry into S-phase of the cell cycle. These regulators include the retinoblastoma tumor suppressor and its related proteins p107 and p130, as well as the CDK inhibitors p21, p27 and p57.
\nMyriad mechanisms account for the inactivation of APC/C at the G1/S boundary, some of which were discussed above. This includes the degradation of Cdh1 by SCFCyclin F and perhaps by the APC/C itself [61, 95]. The APC/C E2 enzymes, Ube2S and Ube2C, are unstable proteins and are also APC/C substrates [4, 96]. The substrate receptor Cdh1 is subject to CDK dependent phosphorylation, preventing its association with the APC/C and likely affecting its localization [89, 97, 98, 99, 100, 101]. Finally, accumulation of Emi1 is controlled by E2F, contributing to APC/C inhibition [16, 80, 84].
\nThe interconnected web of enzymes, substrates, and pathways discussed above paints a complicated picture of G1/S control. Remarkably, our understanding of the role of ubiquitin ligases in S-phase entry pales in comparison to studies performed on parallel kinase signaling cascades that converge on the E2F transcription factor. In quiescent and early G1 cells, E2F activity is repressed by the retinoblastoma tumor suppressor (RB), as well as the RB-like proteins P130 and P107. The phosphorylation of RB, first by Cyclin D-CDK4/6, and then by Cyclin E-Cdk2, inactivates RB and derepresses E2F. This derepression, in turn, triggers the transcriptional upregulation of many genes needed for S-phase entry.
\nHow then do the pathways described above fit together with each other, and with the canonical CDK-RB-E2F pathway? We propose that multiple pathways act coordinately to promote the start of DNA replication. The most well-studied of these is the RB-E2F pathway, which promotes S-phase entry by promoting the expression of numerous cell cycle genes. In parallel, ubiquitin signaling pathways that control the degradation of numerous cell cycle proteins coordinate entry into S-phase. First, SCFSkp2 must be active and able to promote the degradation of CKI proteins. Second, SCFFbw7 must be inactive or otherwise unable to ubiquitinate its substrates Cyclin E and Myc, which accumulate to promote cell cycle. Third, SCFCyclin F must be available to trigger the degradation of Cdh1 and help promote the inactivation of APC/C. And finally, the APC/C must be inactivated, by Cyclin F and other pathways, allowing for the accumulation of cell cycle proteins (many of which are transcribed by E2F), to promote S-phase entry (Figure 7). It is notable that Cyclin F and Skp2, as well as many other cell cycle proteins, are downregulated by APC/C. Altogether, this suggests that aberrant APC/C inactivation could promote cancer cell cycles. Accordingly, single allelic loss of Cdh1 causes cancer in mice [94]. How APC/C might be inactivated in cancer remains an open question of significant importance that has only recently begun to be studied [17].
\nOverview of ubiquitin signaling pathways involved in G1/S. A subset of substrates are shown. Note that the APC/C controls the stability of several dozen substrate proteins during late mitosis and early G1.
Upstream of these regulators are myriad kinase signaling cascades. These kinase cascades include, for example, the phosphorylation of RB by CDK4/6 and also CDK2; phosphorylation of Cyclin F and Skp2 by AKT; and, phosphorylation of Myc and Cyclin E, thereby marking them for degradation by Fbw7. Significantly, we hypothesize that these pathways control S-phase entry by globally remodeling the protein landscape either through changes in gene expression or protein degradation. The activity of CDK2, CDK4/6 and AKT is dysregulated in many cancers. This suggests that dysregulated cell cycle transcription, as well as dysregulated cell cycle ubiquitination, likely contributes to a weakening of the G1/S boundary and uncontrolled cancer cell cycles.
\nTesting this hypothesis and determining how these pathways are integrated remains an important question for future study. Determining the order of and integration between these pathways is also critical. For example, recent live imaging studies demonstrated that CDK2 becomes active in mid-G1, several hours before APC/C is turned off. Moreover, these studies indicate that APC/C inactivation occurs at nearly the same time as DNA replication [16]. What is unclear is how Emi1, Cyclin F, and Skp2 accumulate at this time, as these proteins have never before been studied together in the same experimental system. In addition, the overwhelming majority of studies that have interrogated the kinetics of their accumulation have relied on bulk biochemical measurements (immunoblots) in synchronized cells. While informative, these studies would be better undertaken in asynchronous cells using either immunofluorescence or live cell reporters. Further, CDK2 activity begins to increase many hours before the inactivation of APC/C. It is therefore unknown how APC/C remains active into late G1-phase and is protected from CDK-dependent inactivation. Resolving these important questions will provide insight regarding how cells breach the G1/S boundary during the homeostatic cell cycles that occur during organismal development and growth, or in response to cell damage or wounding. Importantly, the G1/S boundary is universally dysfunctional in cancer and is the target of therapeutic interventions in the treatment of disease. Therefore, unraveling the complex pathways and mechanisms by which the ubiquitin system contributes to G1/S will shed light on both the etiology and treatment of cancer in the future.
\nSpecial thanks go to the Emanuele laboratory for feedback. Work in the Emanuele lab is supported by start-up funds from the University Cancer Research Fund and The National Institute of General Medical Sciences (NIH; R01GM120309).
\nThe authors declare no competing conflicts of interest.
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Besides, these parts are not only about cutting-edge technologies, but also related with conventional methods and their new applications in colored wastewater treatment area briefly.",book:{id:"5086",slug:"textile-wastewater-treatment",title:"Textile Wastewater Treatment",fullTitle:"Textile Wastewater Treatment"},signatures:"Serkan Arslan, Murat Eyvaz, Ercan Gürbulak and Ebubekir Yüksel",authors:[{id:"170083",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Eyvaz",slug:"murat-eyvaz",fullName:"Murat Eyvaz"},{id:"176699",title:"Dr.",name:"Ercan",middleName:null,surname:"Gürbulak",slug:"ercan-gurbulak",fullName:"Ercan Gürbulak"},{id:"176700",title:"MSc.",name:"Serkan",middleName:null,surname:"Arslan",slug:"serkan-arslan",fullName:"Serkan Arslan"},{id:"176701",title:"Prof.",name:"Ebubekir",middleName:null,surname:"Yüksel",slug:"ebubekir-yuksel",fullName:"Ebubekir Yüksel"}]},{id:"42001",doi:"10.5772/53777",title:"Cyclodextrins in Textile Finishing",slug:"cyclodextrins-in-textile-finishing",totalDownloads:5486,totalCrossrefCites:19,totalDimensionsCites:39,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Bojana Voncina and Vera Vivod",authors:[{id:"33838",title:"Prof.",name:"Bojana",middleName:null,surname:"Voncina",slug:"bojana-voncina",fullName:"Bojana Voncina"}]},{id:"41409",doi:"10.5772/53911",title:"Surface Modification Methods for Improving the Dyeability of Textile Fabrics",slug:"surface-modification-methods-for-improving-the-dyeability-of-textile-fabrics",totalDownloads:7061,totalCrossrefCites:13,totalDimensionsCites:36,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Sheila Shahidi, Jakub Wiener and Mahmood Ghoranneviss",authors:[{id:"58854",title:"Dr.",name:null,middleName:null,surname:"Shahidi",slug:"shahidi",fullName:"Shahidi"}]},{id:"68157",doi:"10.5772/intechopen.87968",title:"Introductory Chapter: Textile Manufacturing Processes",slug:"introductory-chapter-textile-manufacturing-processes",totalDownloads:4473,totalCrossrefCites:14,totalDimensionsCites:26,abstract:null,book:{id:"8892",slug:"textile-manufacturing-processes",title:"Textile Manufacturing Processes",fullTitle:"Textile Manufacturing Processes"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]}],mostDownloadedChaptersLast30Days:[{id:"68157",title:"Introductory Chapter: Textile Manufacturing Processes",slug:"introductory-chapter-textile-manufacturing-processes",totalDownloads:4488,totalCrossrefCites:16,totalDimensionsCites:27,abstract:null,book:{id:"8892",slug:"textile-manufacturing-processes",title:"Textile Manufacturing Processes",fullTitle:"Textile Manufacturing Processes"},signatures:"Faheem Uddin",authors:[{id:"228107",title:"Prof.",name:"Faheem",middleName:null,surname:"Uddin",slug:"faheem-uddin",fullName:"Faheem Uddin"}]},{id:"41411",title:"Textile Dyes: Dyeing Process and Environmental Impact",slug:"textile-dyes-dyeing-process-and-environmental-impact",totalDownloads:20676,totalCrossrefCites:101,totalDimensionsCites:320,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Farah Maria Drumond Chequer, Gisele Augusto Rodrigues de Oliveira, Elisa Raquel Anastácio Ferraz, Juliano Carvalho Cardoso, Maria Valnice Boldrin Zanoni and Danielle Palma de Oliveira",authors:[{id:"49040",title:"Prof.",name:"Danielle",middleName:null,surname:"Palma De Oliveira",slug:"danielle-palma-de-oliveira",fullName:"Danielle Palma De Oliveira"},{id:"149074",title:"Prof.",name:"Maria Valnice",middleName:null,surname:"Zanoni",slug:"maria-valnice-zanoni",fullName:"Maria Valnice Zanoni"},{id:"153502",title:"Ph.D.",name:"Farah",middleName:null,surname:"Chequer",slug:"farah-chequer",fullName:"Farah Chequer"},{id:"153504",title:"MSc.",name:"Gisele",middleName:null,surname:"Oliveira",slug:"gisele-oliveira",fullName:"Gisele Oliveira"},{id:"163377",title:"Dr.",name:"Juliano",middleName:null,surname:"Cardoso",slug:"juliano-cardoso",fullName:"Juliano Cardoso"},{id:"163393",title:"Dr.",name:"Elisa",middleName:null,surname:"Ferraz",slug:"elisa-ferraz",fullName:"Elisa Ferraz"}]},{id:"49647",title:"Fiber Selection for the Production of Nonwovens",slug:"fiber-selection-for-the-production-of-nonwovens",totalDownloads:10568,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"The most significant feature of nonwoven fabric is made directly from fibers in a continuous production line. While manufacturing nonwovens, some conventional textile operations, such as carding, drawing, roving, spinning, weaving or knitting, are partially or completely eliminated. For this reason the choice of fiber is very important for nonwoven manufacturers. The commonly used fibers include natural fibers (cotton, jute, flax, wool), synthetic fibers (polyester (PES), polypropylene (PP), polyamide, rayon), special fibers (glass, carbon, nanofiber, bi-component, superabsorbent fibers). Raw materials have not only delivered significant product improvements but also benefited people using these products by providing hygiene and comfort.",book:{id:"5062",slug:"non-woven-fabrics",title:"Non-woven Fabrics",fullTitle:"Non-woven Fabrics"},signatures:"Nazan Avcioglu Kalebek and Osman Babaarslan",authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",slug:"osman-babaarslan",fullName:"Osman Babaarslan"},{id:"175829",title:"Dr.",name:"Nazan",middleName:null,surname:"Kalebek",slug:"nazan-kalebek",fullName:"Nazan Kalebek"}]},{id:"41409",title:"Surface Modification Methods for Improving the Dyeability of Textile Fabrics",slug:"surface-modification-methods-for-improving-the-dyeability-of-textile-fabrics",totalDownloads:7063,totalCrossrefCites:13,totalDimensionsCites:36,abstract:null,book:{id:"3137",slug:"eco-friendly-textile-dyeing-and-finishing",title:"Eco-Friendly Textile Dyeing and Finishing",fullTitle:"Eco-Friendly Textile Dyeing and Finishing"},signatures:"Sheila Shahidi, Jakub Wiener and Mahmood Ghoranneviss",authors:[{id:"58854",title:"Dr.",name:null,middleName:null,surname:"Shahidi",slug:"shahidi",fullName:"Shahidi"}]},{id:"55424",title:"Textile Reinforced Structural Composites for Advanced Applications",slug:"textile-reinforced-structural-composites-for-advanced-applications",totalDownloads:3876,totalCrossrefCites:9,totalDimensionsCites:16,abstract:"Textile-reinforced composites are increasingly used in various industries such as aerospace, construction, automotive, medicine, and sports due to their distinctive advantages over traditional materials such as metals and ceramics. Fiber-reinforced composite materials are lightweight, stiff, and strong. They have good fatigue and impact resistance. Their directional and overall properties can be tailored to fulfill specific needs of different end uses by changing constituent material types and fabrication parameters such as fiber volume fraction and fiber architecture. A variety of fiber architectures can be obtained by using two- (2D) and three-dimensional (3D) fabric production techniques such as weaving, knitting, braiding, stitching, and nonwoven methods. Each fiber architecture/textile form results in a specific configuration of mechanical and performance properties of the resulting composites and determines the end-use possibilities and product range. This chapter highlights the constituent materials, fabric formation techniques, production methods, as well as application areas of textile-reinforced composites. Fiber and matrix materials used for the production of composite materials are outlined. Various textile production methods used for the formation of textile preforms are explained. Composite fabrication methods are introduced. Engineering properties of textile composites are reviewed with regard to specific application areas. The latest developments and future challenges for textile-reinforced composites are presented.",book:{id:"5921",slug:"textiles-for-advanced-applications",title:"Textiles for Advanced Applications",fullTitle:"Textiles for Advanced Applications"},signatures:"Nesrin Sahbaz Karaduman, Yekta Karaduman, Huseyin Ozdemir\nand Gokce Ozdemir",authors:[{id:"175839",title:"Ph.D.",name:"Nesrin",middleName:null,surname:"Sahbaz Karaduman",slug:"nesrin-sahbaz-karaduman",fullName:"Nesrin Sahbaz Karaduman"},{id:"201620",title:"Dr.",name:"Yekta",middleName:null,surname:"Karaduman",slug:"yekta-karaduman",fullName:"Yekta Karaduman"},{id:"201621",title:"Dr.",name:"Hüseyin",middleName:null,surname:"Özdemir",slug:"huseyin-ozdemir",fullName:"Hüseyin Özdemir"},{id:"201622",title:"Dr.",name:"Gökce",middleName:null,surname:"Özdemir",slug:"gokce-ozdemir",fullName:"Gökce Özdemir"}]}],onlineFirstChaptersFilter:{topicId:"1376",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},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:"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"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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