Overview of specific knowledge needed in the drug life cycle.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5189",leadTitle:null,fullTitle:"Sustainable Supply Chain Management",title:"Sustainable Supply Chain Management",subtitle:null,reviewType:"peer-reviewed",abstract:"The book is a collection of studies dedicated to different perspectives of three dimensions or pillars of the sustainability of supply chain and supply chain management - economic, environmental, and social - and other aspects related to performance evaluation, optimization, and modelling of and for sustainable supply chain management, and thus presents another valuable contribution to sustainable development and sustainable way of life.",isbn:"978-953-51-2434-4",printIsbn:"978-953-51-2433-7",pdfIsbn:"978-953-51-5149-4",doi:"10.5772/61491",price:119,priceEur:129,priceUsd:155,slug:"sustainable-supply-chain-management",numberOfPages:276,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"bb451bb6037023b54ee65e9fd80e83c9",bookSignature:"Evelin Krmac",publishedDate:"June 30th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5189.jpg",numberOfDownloads:21610,numberOfWosCitations:12,numberOfCrossrefCitations:11,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:21,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:44,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 13th 2015",dateEndSecondStepPublish:"November 3rd 2015",dateEndThirdStepPublish:"February 7th 2016",dateEndFourthStepPublish:"May 7th 2016",dateEndFifthStepPublish:"June 6th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"32772",title:"Dr.",name:"Evelin",middleName:null,surname:"Krmac",slug:"evelin-krmac",fullName:"Evelin Krmac",profilePictureURL:"https://mts.intechopen.com/storage/users/32772/images/4667_n.jpg",biography:"Dr. Evelin Krmac has a PhD in computer and information science. She is Assistant Professor in the business informatics field at the Faculty of Maritime Studies and Transport, University of Ljubljana, Slovenia, where she is a course manager for Computer and Information Science, Information Science in Traffic, and Information Support of Logistics. Her research interests include the application of Information and Communication Technologies (ICT) in logistics, supply chains and transport, intelligent transport systems, and application of ICT in the learning and teaching process.\nThrough her career, she has actively been contributing in organizing various professional and scientific meetings, in co-editing international scientific journals (such as MEST and FBIM Transactions), in publishing in fields relating to her research interests, and being involved in various scientific research projects.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"457",title:"Supply Chain Management",slug:"engineering-management-supply-chain-management"}],chapters:[{id:"50253",title:"Economic Performance, Greenhouse Gas Emissions, Environmental Management, and Supply Chains in India: A Comparison with Japan",doi:"10.5772/62535",slug:"economic-performance-greenhouse-gas-emissions-environmental-management-and-supply-chains-in-india-a-",totalDownloads:1663,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Using input–output tables and data on wastes from the Japanese industrial sectors, we have provided empirical evidence that, in Japan environmental performance of their upstream suppliers contributes positively to the performance of their final product assembly firms or economic sectors. In this paper, we propose to investigate the same hypothesis for firms and other establishments in manufacturing and other sectors in India. Indian supplier firms that sell goods and services to their client assembler firms are not generally structured in the form of efficient supply chains as in advanced economies. So, the environmental performance of these suppliers may not have positive impacts on the performance of their assembler firms or economic sectors, but this is yet to be verified empirically.",signatures:"Hitoshi Hayami, Masao Nakamura and Kazushige Shimpo",downloadPdfUrl:"/chapter/pdf-download/50253",previewPdfUrl:"/chapter/pdf-preview/50253",authors:[{id:"180369",title:"Prof.",name:"Masao",surname:"Nakamura",slug:"masao-nakamura",fullName:"Masao Nakamura"},{id:"180914",title:"Prof.",name:"Hitoshi",surname:"Hayami",slug:"hitoshi-hayami",fullName:"Hitoshi Hayami"},{id:"180915",title:"Prof.",name:"Kazushige",surname:"Shimpo",slug:"kazushige-shimpo",fullName:"Kazushige Shimpo"}],corrections:null},{id:"50220",title:"Identification of Environmental Criteria for Selecting a Logistics Service Provider: A Step Forward towards Green Supply Chain Management",doi:"10.5772/62533",slug:"identification-of-environmental-criteria-for-selecting-a-logistics-service-provider-a-step-forward-t",totalDownloads:2420,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Green environmental performance increases the competitiveness of the supply chain. However, the greening of the supply chain depends on the manufacturer who drives the green initiative, as well as on all the members of the supply chain who take part in the process. The manufacturer’s attention has been largely focused on the environmental performance of the supplier and retailer, whereas logistics service providers have been somehow neglected. It is, in fact, the case is that logistics service providers have begun to play a critical role in supply chain management and could therefore significantly improve environmental sustainability. They have already undertaken a green initiative that unfortunately has rarely, if at all, been required by the manufacturer. The lack of requirements for logistics providers hinders the progress of a green initiative. To take a step forward towards green supply chain management, this chapter aims to introduce all the necessary criteria for the selection of a logistics service provider (LP), with an emphasis on environmental criteria. The environmental selection criteria, with all related subcriteria, were achieved on the basis of a systematic literature review. It has been found that buyers of logistics services still strive to minimize costs, expect quality logistics services, a well-positioned LP, all the while overlooking environmental issues. The most frequently applied environmental selection criteria are value-added reverse logistics services, followed by environmental expenditures, pollutants released, energy consumption, clean materials and energy use. The findings presented here are useful particularly for researchers, as issues regarding sustainable LP selection and its limitations are highlighted, related to selection criteria identification. These findings may be of less use to managers. However, future phases of this study, richer for the evaluation of logistics experts, will be much more applicable to buyers and providers of logistics services.",signatures:"Patricija Bajec and Danijela Tuljak-Suban",downloadPdfUrl:"/chapter/pdf-download/50220",previewPdfUrl:"/chapter/pdf-preview/50220",authors:[{id:"172904",title:"Dr.",name:"Patricija",surname:"Bajec",slug:"patricija-bajec",fullName:"Patricija Bajec"},{id:"172905",title:"Dr.",name:"Danijela",surname:"Tuljak-Suban",slug:"danijela-tuljak-suban",fullName:"Danijela Tuljak-Suban"}],corrections:null},{id:"51019",title:"Analysing the Adoption of Energy-Saving Technologies in Manufacturing Firms",doi:"10.5772/62852",slug:"analysing-the-adoption-of-energy-saving-technologies-in-manufacturing-firms",totalDownloads:1721,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The present book chapter aims to (i) map the adoption of energy-saving technologies (EST) in manufacturing and (ii) identify structural and operational characteristics that are expected to correlate with EST implementation. The empirical evidence is collected through the European Manufacturing Survey. The analysis presented corresponds to the Spanish subsample 2012 edition. Our main result points to a relatively low implementation of EST, also interpretable as a still unexploited potential these technologies have for manufacturers. Other main findings show (i) a relatively still modest implementation of most EST and (ii) a possible relationship between high implementation of EST and perceived energy efficiency as a consequence of implementation. The chapter draws implications for practice and research.",signatures:"Marc Pons, Josep Llach and Andrea Bikfalvi",downloadPdfUrl:"/chapter/pdf-download/51019",previewPdfUrl:"/chapter/pdf-preview/51019",authors:[{id:"179518",title:"Mr.",name:"Marc",surname:"Pons",slug:"marc-pons",fullName:"Marc Pons"},{id:"180127",title:"Dr.",name:"Josep",surname:"Llach",slug:"josep-llach",fullName:"Josep Llach"},{id:"180965",title:"Dr.",name:"Andrea",surname:"Bikfalvi",slug:"andrea-bikfalvi",fullName:"Andrea Bikfalvi"}],corrections:null},{id:"50485",title:"Fuel Cell as Range Extender in Battery Electric Vehicles for Supply Chain Fleets",doi:"10.5772/62792",slug:"fuel-cell-as-range-extender-in-battery-electric-vehicles-for-supply-chain-fleets",totalDownloads:2531,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The aim of this chapter is to present an outlook about implementation of a range extender system based on fuel cells for battery electric vehicles. Such a system is highly feasible to be implemented in electric vehicles, in particular those used by beverage industry in city centres. The tourism is another industry that uses electric vehicles, for instance in resorts, hotels, airports, zoos, etc. As well, public transportation is another sector involved with this vehicular technology. These sectors are all the time looking for high efficiency and low costs; however, they also need to extend the range of the vehicles to fulfill some logistics requirements in a route. This chapter presents a numerical example for illustrating an implementation of fuel cell range extender system. Advantages, disadvantages, and business opportunities in fuel cell technology are presented.",signatures:"Javier De La Cruz Soto and Ulises Cano Castillo",downloadPdfUrl:"/chapter/pdf-download/50485",previewPdfUrl:"/chapter/pdf-preview/50485",authors:[{id:"155195",title:"Dr.",name:"Ulises",surname:"Cano",slug:"ulises-cano",fullName:"Ulises Cano"},{id:"179785",title:"Dr.",name:"Javier",surname:"De La Cruz Soto",slug:"javier-de-la-cruz-soto",fullName:"Javier De La Cruz Soto"}],corrections:null},{id:"50321",title:"Food Supply Chain: A Review of Approaches Which Enhance Sustainability with a Focus on Social Responsibility",doi:"10.5772/62536",slug:"food-supply-chain-a-review-of-approaches-which-enhance-sustainability-with-a-focus-on-social-respons",totalDownloads:1843,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The sustainability of food supply chain management in a global market after the Economic Crisis is increasingly relevant; the economic and environmental pillars have been closely studied and examined, while the social pillar is considered only marginally and never independently. We propose a literature review focused on 28 articles regarding sustainability in the food supply chain. The proposed review (a) detects methods that could be used to enhance sustainability, (b) highlights the most used methods and their shortcomings, and with regard to social sustainability (c) highlights the fact that most of the studies were found to be based on empirical approach. Moreover, we propose the use of a fuzzy framework to evaluate sustainability (in particular, the social aspect), since fuzzy variables could better explain phenomena and situations generally described verbally.",signatures:"Danijela Tuljak-Suban",downloadPdfUrl:"/chapter/pdf-download/50321",previewPdfUrl:"/chapter/pdf-preview/50321",authors:[{id:"172905",title:"Dr.",name:"Danijela",surname:"Tuljak-Suban",slug:"danijela-tuljak-suban",fullName:"Danijela Tuljak-Suban"}],corrections:null},{id:"50995",title:"Environmental and Social Sustainability in the Fresh Fruit and Vegetables Supply Chain: A Competitiveness’ Asset",doi:"10.5772/63377",slug:"environmental-and-social-sustainability-in-the-fresh-fruit-and-vegetables-supply-chain-a-competitive",totalDownloads:2052,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"The concern for products that meet the requirements of sustainability is a key factor that drives consumers and can be the engine of a successful economy in the food businesses. In the specific case of the fresh fruit and vegetables, more than ever, sustainability understood as a greater focus on the social and environmental performance of the product and of its supply chain, can be considered as a tool to counter the consumer's disaffection. The communication of the product's sustainability can indeed represent a tool to bring out the fruit and vegetable products from the anonymity, a strategy to will make it ‘remember', relying not only on the traditional values recognized to the segment, but also on a set of the supply chain attributes that can differentiate it. However, how to get effectively to the consumer by using a multidimensional and complex concept as the product's sustainability of the product, how to make the sustainability attribute a factor to be considered in the final purchasing choices, how to involve the different stakeholders in the building of a sustainable supply chain (regardless of its length) are still open discussion topics. After presenting the main sustainability certification and communication tools adopted till nowadays for the fresh fruit and vegetables supply chain, the chapter investigates the relative potentialities and criticisms in order to turn them into a real competitiveness’ asset.",signatures:"Nadia Tecco, Nicole Giuggioli, Vincenzo Girgenti and Cristiana\nPeano",downloadPdfUrl:"/chapter/pdf-download/50995",previewPdfUrl:"/chapter/pdf-preview/50995",authors:[{id:"179865",title:"Ph.D.",name:"Nicole",surname:"Giuggioli",slug:"nicole-giuggioli",fullName:"Nicole Giuggioli"},{id:"179987",title:"Dr.",name:"Cristiana",surname:"Peano",slug:"cristiana-peano",fullName:"Cristiana Peano"},{id:"181109",title:"Ph.D.",name:"Nadia",surname:"Tecco",slug:"nadia-tecco",fullName:"Nadia Tecco"},{id:"181111",title:"Ph.D.",name:"Vincenzo",surname:"Girgenti",slug:"vincenzo-girgenti",fullName:"Vincenzo Girgenti"}],corrections:null},{id:"51110",title:"Performance Evaluation for the Sustainable Supply Chain Management",doi:"10.5772/63065",slug:"performance-evaluation-for-the-sustainable-supply-chain-management",totalDownloads:2994,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Supply chain SC activities transform natural resources, raw materials, and components into various finished products that are delivered to end customers. A high efficient SC would bring great benefits to an enterprise such as integrated resources, reduced logistics costs, improved logistics efficiency, and high quality of overall level of services. In contrast, an inefficient SC will bring additional transaction costs, information management costs, and resource waste, reduce the production capacity of all enterprises on the chain, and unsatisfactory customer relationships. So the evaluation of a SC is important for an enterprise to survive in a competitive market in a globalized business environment. Therefore, it is important to research the various methods, performance indicator systems, and technology for evaluating, monitoring, predicting, and optimizing the performance of a SC. A typical procedure of the performance evaluation (PE) of a SC is to use the established evaluation performance indicators, employ an analytical method, follow a given procedure, to carry out quantitatively or qualitatively comparative analysis to provide the objective and accurate evaluation of a SC performance in a selected operation period. Various research works have been carried out in proposing the performance indicator systems and methods for SC performance evaluations. But there are no widely accepted indicator systems that can be applied in practical SC performance evaluations due to the fact that the indicators in different systems have been defined without a common understanding of the meanings and the relationships between them, and they are nonlinear and very complicated.",signatures:"Xuemei Fan and Shujun Zhang",downloadPdfUrl:"/chapter/pdf-download/51110",previewPdfUrl:"/chapter/pdf-preview/51110",authors:[{id:"180918",title:"Dr.",name:"Xuemei",surname:"Fan",slug:"xuemei-fan",fullName:"Xuemei Fan"},{id:"180955",title:"Prof.",name:"Shujun",surname:"Zhang",slug:"shujun-zhang",fullName:"Shujun Zhang"}],corrections:null},{id:"50199",title:"Modeling Sustainable Supply Chain Management as a Complex Adaptive System: The Emergence of Cooperation",doi:"10.5772/62534",slug:"modeling-sustainable-supply-chain-management-as-a-complex-adaptive-system-the-emergence-of-cooperati",totalDownloads:2608,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The aim of this chapter is to characterize sustainable supply chain management as a complex adaptive system (CAS) and develop an evolutionary game theory-based model to understand how cooperation emerges from interactions among companies to adopt sustainable management practices. We consider two interacting populations 1 and 2, each one with heterogeneous companies belonging to the same supply chain. One population is expected to behave cooperatively in adopting sustainable management practices while the other is expected to behave uncooperatively. The mathematical model we propose is game-dynamical replicator equations for multiple populations in the prisoner´s dilemma (PD) game and we implement it using NetLogo software. The proportion of cooperative companies in each population that adopt sustainable management practices evolves positively over time as companies only imitate the adoption of sustainable management practices in their own population and in the populations of their partners when the benefit obtained by cooperating is maximum. The spatial patterns observed help us to clarify the preconditions for the emergence of cooperation among companies in managing material, information and capital flows in a sustainable way. Finally, our simulation results show that the sustainable management of supply chains needs to be studied as CASs, in order to take into account the social side of sustainability.",signatures:"Aida Huerta Barrientos and Idalia Flores de la Mota",downloadPdfUrl:"/chapter/pdf-download/50199",previewPdfUrl:"/chapter/pdf-preview/50199",authors:[{id:"180108",title:"Prof.",name:"Aida",surname:"Huerta Barrientos",slug:"aida-huerta-barrientos",fullName:"Aida Huerta Barrientos"},{id:"185248",title:"Dr.",name:"Idalia",surname:"Flores De La Mota",slug:"idalia-flores-de-la-mota",fullName:"Idalia Flores De La Mota"}],corrections:null},{id:"50354",title:"Energy Chains Optimization for Selection of Sustainable Energy Supply",doi:"10.5772/62537",slug:"energy-chains-optimization-for-selection-of-sustainable-energy-supply",totalDownloads:2034,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The notion of energy chain concept has been defined as the trajectory of energy transformations from the fuel source or energy sources to useful energy form to end users. Production of fuels, heat and electricity from different sources is defined by the appropriate energy supply chain. Every single energy supply chain can be uniquely defined by several sustainability criteria. These criteria are: total energy efficiency of production, total exergy efficiency of overall chain, the coefficient of exergy quality for different products at energy chains, economy of production, investment and environmental criteria. Optimal energy supply chain can be chosen by using multicriteria optimization which fulfils the above-mentioned sustainability criteria. This selected energy chain is close to ideal solution. The ideal energy supply chain is formed from the set of energy production ways which are defined from the perspective of sustainability criteria and which have connection with the current status of technologies, economic, environmental parameters, etc. The concept of optimization in practice is usually based on economics until recently, often neglecting all the other consequences of such a decision. Therefore, multicriteria decision making (MCDM) improves the opportunities in assessing the optimal variant of energy chain for defined ranking criteria. Before the optimization process, it is necessary to create a mathematical model for calculation of optimization criteria. Also, for each specific case of energy production, it is necessary to develop appropriate mathematical formulas to describe the energy chain. Numerical verification, all mathematical calculations and modelling have been applied and confirmed on wood biomass supply chain for energy production in this case. The reason for this is complexity of supply chains in the bioenergy and representation of renewable energy sources. For total ranking of energy chain for production of fuel or energy and selection of optimum variant, the multicriteria optimization and VIKOR method were applied. The significance of energy production from renewable energy sources is particularly expressed nowadays. Basically, the most significant part in the process of energy production from energy sources is the supply chain, final conversion of energy in useful form at the energy plant and the distribution process to end users. Due to the fact that there are various opportunities for the composition of energy chains of fuel supply and different ways of energy production, it is necessary to try to make a unique mathematical approach for this problem. With the proposed sustainability criteria and developed mathematical model, it is possible to unify the overall problem of energy supply chains’ optimization. The proposed developed method can be used for the optimization of any kind of energy supply chains (electricity, heat, fuels or their mix). All of these are enabled by proper selection criteria for the description of overall energy transformations in energy chains and quality evaluation of the energy produced. The developed approach and mathematical model have a very practical application in the selection of optimal variant of energy production and of course in designing new energy chains.",signatures:"Srđan Vasković, Petar Gvero, Vlado Medaković and Velid Halilović",downloadPdfUrl:"/chapter/pdf-download/50354",previewPdfUrl:"/chapter/pdf-preview/50354",authors:[{id:"141823",title:"Prof.",name:"Petar",surname:"Gvero",slug:"petar-gvero",fullName:"Petar Gvero"},{id:"180821",title:"Ph.D.",name:"Srdjan",surname:"Vaskovic",slug:"srdjan-vaskovic",fullName:"Srdjan Vaskovic"},{id:"180982",title:"Dr.",name:"Vlado",surname:"Medakovic",slug:"vlado-medakovic",fullName:"Vlado Medakovic"},{id:"180983",title:"Dr.",name:"Velid",surname:"Halilovic",slug:"velid-halilovic",fullName:"Velid Halilovic"}],corrections:null},{id:"50487",title:"Support International Business Expansion with Sequential Reviews",doi:"10.5772/62987",slug:"support-international-business-expansion-with-sequential-reviews",totalDownloads:1747,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter is about the multinational company’s decision on whether to enter new foreign markets using direct investment, exporting, or developing a local partner for distribution, with the possibility of scaling the investment under different demand levels. The perception of the host market demand does not remain the same during the investment period due to additional information and economic or political reasons. Therefore, the influence of uncertainty can be addressed by recombining a trinomial lattice model with changing uncertainty, to value investments with several interacting options. Overall, in this chapter we enhance the knowledge associated with exploring foreign markets subject to different demand uncertainties, valuing the flexibility of sequential options.",signatures:"Rui Fernandes and Carlos Pinho",downloadPdfUrl:"/chapter/pdf-download/50487",previewPdfUrl:"/chapter/pdf-preview/50487",authors:[{id:"148780",title:"Prof.",name:"Carlos",surname:"Pinho",slug:"carlos-pinho",fullName:"Carlos Pinho"},{id:"180385",title:"Prof.",name:"Rui",surname:"Fernandes",slug:"rui-fernandes",fullName:"Rui Fernandes"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8603",title:"Green Practices and Strategies in Supply Chain Management",subtitle:null,isOpenForSubmission:!1,hash:"cfd8838aeddebe04b84b2fbc553b6887",slug:"green-practices-and-strategies-in-supply-chain-management",bookSignature:"Syed Abdul Rehman Khan",coverURL:"https://cdn.intechopen.com/books/images_new/8603.jpg",editedByType:"Edited by",editors:[{id:"254664",title:"Prof.",name:"Syed Abdul Rehman",surname:"Khan",slug:"syed-abdul-rehman-khan",fullName:"Syed Abdul Rehman Khan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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\nThe drug life cycle is usually subdivided into discovery research, development and commercialisation and spans the whole trajectory from idea to patients, from bench to market (withdrawal).
\nThe professional field covers the whole pharmaceutical sector, which is not just limited to drugs or to medicines for human or animal use but also includes medical devices, diagnostics, radiopharmaceuticals, nutriceuticals and other related areas of activity. Nor is this sector limited to the (bio-)pharmaceutical industry, but it also includes health authorities, academia and research centres, clinical investigator sites, contract research organisations (CROs) and many more. The need for a highly educated workforce is clearly present in all of these areas and the pharma sector is offering opportunities for a wide spectrum of academic graduates with a Bachelor, a Master, or a PhD degree. Despite the many job opportunities in this sector, competencies of young university graduates are seldom adjusted to the specific requirements listed in the job vacancies. Moreover, they often lack an understanding of the drug development process and the various perspectives it offers for career development.
\nThe aim of this chapter is to give academic graduates a better idea about the many job opportunities over the entire drug life cycle, offered by a wide variety of companies and organisations and for a broad spectrum of qualified professionals.
\nAll the above will be presented in more detail in Sections 2–5 of this chapter.
\nAfter the overview of job opportunities, career perspectives and training opportunities will be discussed in Sections 6 and 7 and important employability elements in Section 8.
\nAs this chapter is primarily targeted at young graduates, Section 9 adds some practical dos and don’ts for effective job application. The chapter ends with some concluding remarks (Section 10) and a bibliography for further reading.
\nThe life cycle of a drug involves essentially three parts: drug discovery and design (research), drug development and drug commercialisation [1]. They are largely consecutive in nature, but some activities are carried out in parallel.
\nDrug research is primarily driven by an unmet medical need, i.e. a therapeutic area in need of a (better) drug. Drugs are either discovered in nature or in existing chemical libraries, or either (semi-)synthesised or designed
During drug development, the potential drug candidate progresses to a drug or a medicinal product which is effective and safe to be administered to humans (or animals) to prevent, diagnose, or treat a disease. It is a complex and highly regulated process, with a lot of intermediate failures, (re-)assessments and (re-)iterations along the long road. Because of these characteristics, drug development is often subdivided in non-clinical and clinical development, as well as in early and late development. In drug development for humans, clinical development includes all experiments with the drug in human subjects (healthy volunteers or patients), while non-clinical development includes all experiments with the drug in animals,
The final part, drug commercialisation, starts with the market authorisation (or drug approval), based on all the available data about quality, efficacy and safety on the medicine and a positive benefit-risk balance in the targeted population, allowing the drug to be marketed and to generate return on investment. But market authorisation (per country, per region like the European Union, or worldwide) is not enough to be successful on the market; there are other hurdles to be taken such as a fair price setting and drug reimbursement by social security systems (based on the added value of the drug for patients and its affordability by society), together known as market access hurdles. Once taken, the drug can be launched and marketing and sales can really start, in parallel with large-scale production and distribution. When the patent of the drug expires (generally 20 years after its application), generic and biosimilar competitors enter the market and the sales of the original drug suddenly drop (the patent cliff), but a drug with added value can still stay on the market for many more years, until it is finally withdrawn. Drug commercialisation is more a world of health economists, marketers, pharmacists, pharmaceutical physicians, sales reps, lawyers and business managers. A schematic representation of the drug life cycle is given in Figure 1.
\nSchematic representation of the drug life cycle. yrs, years.
The (bio-)pharmaceutical industry is probably the biggest employer in this sector worldwide.
\nIt is already a world in itself, as it is an umbrella term with its main representatives being ‘big pharma’ companies, active throughout the whole value chain of the drug life cycle. They research, develop, manufacture and market innovative medicines, either the more classic small molecules or the more recently introduced large biopharmaceuticals such as therapeutic proteins and monoclonal antibodies (produced by living organisms or cells). Under the umbrella also operate medtech companies (e.g. medical devices, implants, biomaterials and
However, the pharmaceutical sector is a lot broader than the pharmaceutical industry and offers many additional jobs and career opportunities. Other important organisations, institutions, or actors in this sector are regulatory agencies, such as national or regional medicines agencies (such as the FDA in the USA and the EMA in Europe, granting drug approvals), certified bodies (the equivalent for medical devices), or patent offices; academia, research centres and spin-offs active in basic research, drug discovery and design, but also early drug development; clinical investigator sites, be it phase 1 or clinical pharmacology units (CPUs) either university- or CRO-owned, university or regional hospitals, site management organisations (SMOs), or the European Organisation for the Research and Treatment of Cancer (EORTC); patient organisations; non-profit drug research funders such as the Bill and Melinda Gates Foundation; consultants, lobbyists and law firms; venture capitalists and investment banks; entrepreneurs and self-employed persons; and many more…
\nOverall, the pharmaceutical sector offers a wealth of job opportunities and career perspectives for young and talented graduates of the necessary calibre and commitment.
\nIn this section, we walk through the drug life cycle and focus on job opportunities that are specific to the different parts of the cycle. Support functions that are important over the entire cycle are presented in Section 5.
\nDrug discovery research is either phenotypic-based (empirical and response-driven) or target-based (molecular and hypothesis-driven). Although the phenotypic-based approach has been very successful in the past, today’s drug discovery is more target-based. The process is as follows: (1) selection and validation of a (druggable) target, mostly a protein (e.g. receptor, enzyme, ion-channel and antigen), but also carriers of genetic information (e.g. DNA/RNA and oncogenes); (2) development and validation of a proper assay, allowing to study the interaction between the target and potential drug candidates; (3) (high-throughput) screening (HTS) of potential drugs, generated through
Drug discovery research is highly dependent on the interplay between different scientific and other disciplines. In practice, it includes intensive collaboration between mainly:\n
different types of biologists, such as molecular biologists, biochemists, biotechnologists, bioinformaticians and biomedical scientists;
different types of chemists, such as medicinal chemists, combichem specialists, computer-assisted drug designers, protein chemists and analytical chemists;
pharmacologists, pharmacokineticists, pharmacometricians, toxicologists, biopharmacy and pharmaceutical technology experts;
as well as representatives of other disciplines, such as (bio-)engineers, data analysts, intellectual property (IP) specialists and patent lawyers.
Drug research departments may be organised per therapeutic domain (more specialised and more compartmentalised) or rather more ‘holistically’ per biological platform, such as a similar target family (e.g. kinases and ion channels), or a similar biological mechanism (e.g. angiogenesis, inflammation, cell cycle control and epigenetics), or per common technological platform (e.g. 3D modelling, X-ray crystallography and NMR spectroscopy).
\nInnovative drug research organisations (pharmaceutical companies, academic centres, spin-offs, or start-ups) are looking for highly educated and talented individuals with at least a master’s degree and preferably a PhD in the aforementioned disciplines. However, being an excellent scientist is not enough to be successful in this field. You also need the right creative mindset, being able to think out of the box and to work together in a multidisciplinary team on a specific project for several years.
\nDiscovery research is the least regulated phase of the drug life cycle and confers to professionals working in this field a fairly high degree of freedom, although in the competitive world of today, research teams also have to deliver quality products, in time and within budget.
\nAs drug R&D is costly and risky; drug candidates are patented so that they later gain market exclusivity without competition for a set period (in general, 20 years after patent filing). Therefore, drug research organisations as well as national and international patent offices also offer job opportunities for IP specialists, such as patent lawyers and patent reviewers.
\nNon-clinical drug development, including all experiments not involving human subjects, is an umbrella term referring to the following activities: chemical and pharmaceutical development (also known as ‘chempharm’ or ‘chemistry, manufacturing and controls (CMC)’), experimental pharmacology (including safety pharmacology), non-clinical toxicology and non-clinical pharmacokinetics. It is essentially a lab activity, involving
Chemical and pharmaceutical development, including drug (product) manufacturing and drug (product) analysis, offers opportunities especially for analytical and green chemists, chemical or bio-engineers, pharmaceutical technologists and (industrial) pharmacists.
\nNon-clinical efficacy and safety pharmacology units are rather looking for experimental pharmacologists, biomedical, or (bio-)pharmaceutical scientists.
\nNon-clinical pharmaceutical toxicology departments are essentially in need of toxicologists, veterinary surgeons and pathologists, but can also do well with interested biomedical or (bio-)pharmaceutical scientists.
\nNon-clinical pharmacokinetics departments are especially looking for pharmacokineticists, experts in drug metabolism and bio-analytical chemists. As model-based drug development is booming, there is also a high need for pharmacometricians, modelling and simulation experts, or more generally, biomedical or (bio-)pharmaceutical scientists with a sound background in mathematics.
\nFor most executive functions in all the above-cited fields, having a master’s degree is an absolute must and a PhD a big plus, although a lot of lab technicians are also welcome.
\nNon-clinical drug development specialists are also needed in (inter-)national medicines agencies as assessors of the CMC (quality) and the non-clinical (safety) parts of the common technical document (CTD), the international harmonised dossier for application of a marketing authorisation of pharmaceuticals for human and animal use.
\nClinical drug development, defined as all studies involving human subjects, is (because of its complexity and long duration) usually subdivided into different phases. It starts classically with small-scale phase 1 studies, including the First-in-Man or First-in-Human (FiM/FiH) study, the single ascending dose (SAD) and the multiple ascending dose (MAD) studies, usually in healthy volunteers (but sometimes in patients), in order to have a first impression of the safety, pharmacokinetics and pharmacodynamics of the drug in development in humans. Then follows phase 2a, to investigate whether the drug works at all in patients according to the presumed mechanism of action (the so-called Proof-of-Concept or POC study) and to have a preliminary idea about the effective and safe dose range in tens of patients with the intended indication. Nowadays, phase 1 is often preceded by a phase 0 study with a limited number of subjects, with a single radioactive microdose of a limited number of drug candidates in order to help researchers in the selection of the best candidate for further full development. In a more recent classification, the preceding phases are together defined as ‘early’ or ‘exploratory’ clinical drug development. The corresponding ‘late’ or ‘confirmatory’ clinical development phase is then corresponding to the classic phases 2b, 3 and 4. The main objective of phase 2b is proper dose (regimen) finding in hundreds of patients with the targeted disease, whereas phase 3 clinical trials aim at confirming a positive clinical benefit/risk balance versus existing therapies in thousands of patients. If successful after this phase, a marketing authorisation application is filed, allowing the drug, if granted, to be put on the market and generate return on investment. This part of the late development phase is also called the preauthorisation or preapproval phase. Finally, in phase 4 of clinical drug development (the post-authorisation or post-approval phase), the use of the drug in everyday clinical practice is studied, its pharmacovigilance (adverse drug reactions) is (are) monitored and new developments are initiated (for new indications, new associations, or new formulations).
\nClinical drug development also involves many different disciplines, each offering several job opportunities. Within clinical drug development organisations (e.g. pharmaceutical companies and CROs), they are usually grouped in the following departments: Clinical Research, Clinical Operations, Medical Review and Pharmacovigilance, Clinical Biometry and Clinical Services, although names can vary from company to company. Their role is to extensively collaborate with one another and generate all clinical data for the marketing authorisation application (preapproval phase), as well as all clinical data for continued developments in the post-approval phase.
\n\n
\n
The
The
And finally, the
Clinical drug development specialists are also needed in (inter-)national medicines agencies as assessors of the clinical parts of clinical trial or investigational new drug applications (CTA in Europe, IND in USA) and Marketing Authorisation (MA, Europe) or New Drug Applications (NDA, USA).
\nA particular characteristic of clinical drug development is that clinical trials are largely performed in investigational sites that do not belong to the drug development organisation itself. With the notable exception of phase 1 trials, usually performed in phase 1 units with healthy volunteers (of which some are owned by pharmaceutical companies or CROs), clinical trials recruit patients who can only be found in institutions, e.g. (university) hospitals, academic phase 1 units, or nursing homes, or else in private practices of general practitioners or medical specialists. Besides, many (academic) hospitals perform their own clinical (drug) research as investigator-initiated trials (IIT). All these investigational sites also offer a lot of job opportunities as investigator, research physician, research nurse, study coordinator and clinical research pharmacist. Some sites are grouped in site management organizations (SMO) or specific organizations such as the European Organisation for Research and Treatment of Cancer (EORTC) that coordinate clinical trials for their member sites. They too need qualified professionals.
\nThe last part of the drug life cycle and hopefully the longest for many years, is the commercialisation phase. It starts with the marketing authorisation of the new medicine and ends with its withdrawal from the market, thus also ending its life cycle (see Figure 1). During this phase, there is a period that an innovative drug can be on the market without competition thanks to its patent protection and additional exclusivity rights, so that the owner can maximise its return of investment (ROI). Once off-patent, sales in general suddenly drop (the patent cliff) because of the introduction of generics or biosimilars, but may find a new equilibrium for years thereafter.
\nDrug commercialisation activities are mostly the prerogative of pharmaceutical companies, although some can also be subcontracted to CROs. They can be found in the following departments: market access, marketing, medical affairs, production and distribution and sales.
\nA marketing authorisation is not sufficient to get a drug for human use on the market. You also need to negotiate a fair price with different national health authorities (price setting) and to demonstrate added value in order to gain acceptable coverage or reimbursement conditions with different national health insurance system providers. These steps are known as market access hurdles.
\n
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\n
Finally,
Within drug development organisations (e.g. mostly pharmaceutical companies, CROs or specialised start-ups and more rarely academic research centres or spin-offs), all the disciplines described above have to work together with the additional help of data managers, data analysts, (bio-)statisticians, quality management experts, specialists in regulatory sciences/affairs, report writers and planning specialists. The coordination and oversight are kept by project team leaders (who prepare the documents needed for decision-making), while go/no go-decisions are taken by (a team of) senior managers.
\nThese activities in the pharma sector are not only important in a specific part of the drug life cycle, but cover the entire business and value chain. They too offer many job opportunities.
\nAs the pharmaceutical sector is highly regulated, the regulatory affairs department makes sure that their pharmaceutical organisation or company complies with all (inter-)national legislations, regulations and guidelines pertaining to their business (worldwide). They are at the forefront in the negotiations with medicines agencies when asking them for scientific advice, or when discussing with them about the marketing authorisation of a new drug, or when arguing about changes to the Summary of Product Characteristics of a drug (SmPC in Europe, labelling in USA). They also see to it that all regulatory documents, such as clinical trial applications, marketing authorisation applications and variations, as well as drug safety reports are prepared, assembled and send to the appropriate health authorities in due time. Regulatory affairs professionals may be responsible for a country or a geographical region (e.g. Europe, USA, or Asia), or they may be specialised in preapproval or post-approval affairs. Most of them are pharmacists or occasionally other life scientists, often with a post-graduate in regulatory sciences or pharmaceutical medicine.
\nThe quality of all the activities at all the steps and levels throughout the drug life cycle is assured by a quality management system (QMS) that typically consists of a set of rules and regulations (good practices or GxP), translated into standard operational procedures (SOP), the proper application of which is regularly monitored by quality control during operations (by self-control and monitoring) and occasionally checked by audits (by internal or external auditors) and inspections (by regulatory authorities).
\nQuality management professionals oversee that all operational departments comply with the recommended best practices, e.g. good laboratory practices (GLP), good clinical practices (GCP), good manufacturing practices (GMP), good pharmacovigilance practices (GVP), good distribution practices (GDP). Typical quality assurance (QA) activities include SOP writing, training of operational staff and investigator teams in quality management and performing audits from which lessons can be learned for further improvement of activities or processes.
\nQA professionals are usually life scientists, often with a postgraduate degree in quality management and with previous experience in an operational function in the pharmaceutical sector. Inspectors from health authorities are usually pharmacists.
\nAll the activities throughout the drug life cycle generate a lot of study reports, publications, regulatory documents and applications to be written in several languages. Most pharma companies have a scientific and/or medical writing department responsible for that. These departments are populated by life scientists and translators with excellent writing and communication skills. Some of these professionals are self-employed and work as external service providers on a freelance basis.
\nMost pharmaceutical companies have their proper training department or corporate training academy, but there is also a plethora of training opportunities offered by specialised service providers (either in-house or external). Their objective is to provide the induction training to newcomers (including company-specific strategic thinking and knowledge transfer), as well as continuous training and development for all (individuals and teams). Training activities are offered to all operational disciplines throughout the drug life cycle, e.g. to researchers, clinical research associates, project and product managers and sales reps. These learning activities are not only meant to optimise their technical knowledge, but also target as much at the development of their core workplace skills. Trainers come in all shapes and sizes, have different backgrounds and qualifications, should have some expertise in the field to be taught, but most of all should have excellent communication and teaching abilities and should love to work with people. The rest can be learned on the job by training the trainer.
\nThe success of any business depends heavily on the effectiveness of its managers. This is equally true in the complex pharmaceutical sector, where many aspects of management come into play, such as strategic management (e.g. innovation, portfolio or risk management and go/no go decision-making) as well as operational management (e.g. project management, clinical, or sales operations). Therefore, there is a high need for visionary leaders and talented managers in this sector. Some people have inborn leadership and management talents, but others grow in it during their career development. Senior and corporate managers in the pharmaceutical business have different backgrounds and qualifications, from life scientists to economists and lawyers, often with a Master in Business Administration (MBA).
\nAt entry, young professionals are often employed as a junior or an assistant, preceding their functional job title (e.g. Junior or Assistant Project Manager). After a year or two, these prefixes can be dropped and after an additional number of years of experience in the same job the prefix can change to Senior (e.g. Senior Project Manager).
\nInitial on-the-job training and work experience can be gained during traineeships, internships, job or work shadowing, secondments and temp jobs (all paid or not).
\nIn the (bio-)pharmaceutical industry, many young academics start their career as an employee of a CRO, which then outsources them for a certain period (6 months or a year) to a pharmaceutical company for a specific job. After a couple of such secondments in different companies, these young professionals get a better idea of what they really want and what is offered out there for their future career development.
\nAfter an initial work experience of a varying number of years, young professionals usually start thinking of their career development in the pharmaceutical sector. An important element to consider is whether you want to stay an expert in your field or become a manager or a leader, as they require different skills, training and work experience.
\nCareer moves can be of several types:
You can move along the path of the drug life cycle, e.g. you can start in Clinical Operations (as Project Manager) and move to Regulatory Affairs (as Country or Regional Manager) or Marketing (as Product Manager). Moving backwards from marketing to R&D is much harder though.
You can move lateral (e.g. switch in the same position from one country to another) or move up (e.g. become a Project Team Manager or Group Product Manager).
You can start an international career, working in several countries worldwide and then return to the company headquarters for a senior management job.
You can switch from one company to another within the pharmaceutical industry, or you can switch from a CRO to a pharma company, or you can switch back to academia, or start a career in a governmental agency.
With every career move, you confront new challenges and over the years you get more responsibility, eventually as senior manager. The ultimate move may be that you become Chief Executive Officer (CEO), the ‘big boss’ of a company.
\nAs an alternative career option, you can also start your own company, either as a young entrepreneur or as a senior consultant. Both these options require a solid business plan and an entrepreneurial mindset.
\nGiven the high number of job and career opportunities described above, the main challenge for young students and graduates is to understand which are their preferred jobs and how to get them.
\nA useful approach is to attend all possible orientation events such as career days, organised nowadays by most universities in which it is possible to listen to experts coming from different companies.
\n\nSome of the biggest pharmaceutical companies, including Abbott http://www.abbott.com/careers/students/development-programs.html http://www.abbvie.com/careers/student-opportunities/development-programs.html http://careers.amgen.com/university-relations/internships-co-ops/ http://www.astrazenecacareers.com/students/programmes/ http://www.baxter.com/careers/programs/healthcare-internships-co-ops.page https://career.bayer.com/en/career/working-at-bayer/students/ https://www.biogen-international.com/en/careers1/pharmd-fellowships.html http://careers.boehringer-ingelheim.com/students http://www.bms.com/careers/university_recruitment/internships_co-ops/pages/graduates_undergraduates.aspx https://careers.lilly.com/campus http://www.gilead.com/careers/careers/current-opportunities http://futureleaders.gsk.com/en-gb/our-programmes/ http://www.careers.jnj.com/explore-careers-student http://www.merck.com/careers/life-at-merck/students-and-graduates.html http://www.merckgroup.com/en/careers/graduates_and_students/faq/faq.html https://www.novartis.com/careers http://www.novonordisk.com/careers/graduates-students-and-trainees/graduates/graduate-programmes-overview-uk.html http://www.roche.com/careers/switzerland/ch_your_job/students_and_graduates/trainee_programs.htm http://en.sanofi.com/careers/join_sanofi/graduates_interns/graduates_interns.aspx http://www.tevapharm.com/teva_careers/european_leadership_programme/
Useful websites to find excellent scientific positions in public or private institutions are https://www.sciencemag.org/careers, http://www.nature.com/naturejobs/science/, http://jobs.newscientist.com/, etc.
\nAnother valuable strategy is to apply for a traineeship in a company in another European country participating in the Erasmus+ programme. https://ec.europa.eu/programmes/erasmus-plus/node_en https://ec.europa.eu/programmes/erasmus-plus/individuals_en#tab-1-4
Some European Institutions such as the European Medicines Agency (EMA), http://www.ema.europa.eu/ema/index.jsp?curl=pages/about_us/general/general_content_000321.jsp http://ecdc.europa.eu/en/aboutus/jobs/Pages/Traineeships.aspx http://www.epo.org/about-us/jobs/vacancies/internships.html
The Innovative Medicine Initiative (IMI), http://www.imi.europa.eu/
European Medicines Research Training Network http://www.emtrain.eu/
European programme in Pharmacovigilance and Pharmacoepidemiology https://www.eu2p.org/
Pharmaceutical Medicine Training Programme http://www.pharmatrain.eu/
European Modular Education and Training Programme in Safety Sciences for Medicines http://www.safescimet.eu/
Another important question often asked by students and graduates is related to the necessary level of education required for the different positions in the pharmaceutical sector. The answer to it is not always easy because despite the harmonization of the architecture of the European higher education obtained through the Bologna process since 1999 http://ec.europa.eu/education/policy/higher-education/bologna-process_en.htm
Apart from technical qualifications, it is important to develop managerial leadership competences. So how do we know what leadership competences are important to career success? The Association to Advance Collegiate Schools of Business (AACSB) [2], which gives accreditation to business schools, developed a list of “General Skills Areas” that students are expected to develop:
Written and oral communication: able to communicate effectively orally and in writing.
Ethical understanding and reasoning: able to identify ethical issues and address the issues in a socially responsible manner.
Analytical thinking: able to analyse and frame problems.
Information technology: able to use current technologies in business and management contexts.
Interpersonal relations and teamwork: able to work effectively with others and in a team environment.
Diverse and multicultural work environments: able to work effectively in diverse environments.
Reflective thinking: able to understand oneself in the context of society.
Application of knowledge: able to translate knowledge into practice.
Vitae is a non-profit organisation based in Cambridge, UK, with almost 50 years of experience in enhancing the skills and careers of researchers. As a spin-off of these activities, Vitae has developed an Employability Lens that could serve as a researcher development framework for careers outside academia. This tool gives an overview of the key knowledge, behaviours and attributes that are typically important for graduates from academia and as such often appreciated by employers, see link to the pdf below:
\nhttps://www.vitae.ac.uk/vitae-publications/rdf-related/employability-lens-vitae-researcher-development-framework-rdf-may-2012.pdf
\nThe Vitae Employability Lens is particularly useful in identifying additional skills on top of the specific key knowledge of academics seeking employment outside academia, for example, in the drug development field. To achieve this, it especially focuses on behaviours and attitudes, rather than on the knowledge base that has been the original aim of studies and training during academic studies. In doing so, the lens can serve as an ‘eye opener’ especially for PhD holders that primarily expected to valorise their theoretical knowledge and their technical experience. Thanks to this employability lens, a range of transferable skills has been identified that has proved to be added value in almost any workplace, thereby significantly lowering the threshold for academic graduates to make the step towards industry. In addition, these transferable skills can be trained and many Doctoral Schools provide focused short training programs as a way to effectively support the career perspectives of PhD researchers after obtaining their degree.
\nApart from this focus on transferable skills, it can be expected that many academically trained researchers will wonder in what part of the drug life cycle their specific knowledge base could still provide an added value. This would enable them to valorise their specific knowledge and experience and thus provide a basis for a career after making the step from academia towards the pharmaceutical sector. An overview of specific knowledge needed in the Drug Life Cycle is given below in Table 1.
\nAcademic knowledge base for employment | \nDrug life cycle expressed in five stages: | \n|||||
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Academic fields by discipline | \nAcademic degree | \nResearch discovery & design | \nNon-clinical development | \nEarly clinical development | \nLate clinical development | \nCommercialisation | \n
Pharmaceutical sciences | \nMA | \n\n | × | \n\n | × | \n× | \n
Pharmaceutical sciences | \nPhD | \n×× | \n×× | \n× | \n\n | \n |
Medical sciences | \nMD | \n\n | \n | × | \n× | \n× | \n
Medical sciences | \nMD-PhD | \n×× | \n× | \n×× | \n× | \n\n |
Biomedical sciences | \nMA | \n\n | \n | \n | × | \n× | \n
Biomedical sciences | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Veterinary sciences | \nMA | \n× | \n× | \n\n | \n | \n |
Veterinary sciences | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Pharmacy | \nMA | \n\n | × | \n× | \n× | \n\n |
Pharmacy | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Industrial pharmacy | \nMA | \n\n | × | \n× | \n× | \n× | \n
Industrial pharmacy | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Biotechnologies | \nMA | \n\n | × | \n\n | × | \n× | \n
Biotechnologies | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Chemistry | \nMA | \n\n | × | \n\n | \n | \n |
Chemistry | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Biology | \nMA | \n\n | \n | \n | \n | \n |
Biology | \nPhD | \n×× | \n×× | \n\n | \n | \n |
Biochemistry | \nMA | \n\n | \n | \n | \n | \n |
Biochemistry | \nPhD | \n× | \n×× | \n\n | \n | \n |
Physics | \nMA | \n\n | \n | \n | \n | \n |
Physics | \nPhD | \n× | \n× | \n\n | \n | \n |
(Bio)informatics | \nMA | \n× | \n× | \n\n | \n | \n |
(Bio)informatics | \nPhD | \n×× | \n× | \n\n | \n | \n |
Engineering | \nMA | \n\n | × | \n\n | \n | × | \n
Engineering | \nPhD | \n× | \n× | \n× | \n× | \n\n |
Mathematics and data analysis | \nMA/PhD | \n× | \n× | \n× | \n× | \n\n |
Law and legal studies | \nMA | \n× | \n× | \n× | \n× | \n×× | \n
Economy and finance | \nMA | \n\n | \n | \n | \n | × | \n
Business administration | \nMA (MBA) | \n\n | \n | \n | \n | × | \n
Communication studies | \nMA/PhD | \n\n | \n | \n | × | \n× | \n
Languages | \nMA | \n\n | \n | \n | × | \n× | \n
Overview of specific knowledge needed in the drug life cycle.
In Table 1, the academic knowledge base for employment has been linked to the various stages of the drug life cycle, as introduced in the beginning of this chapter. The clinical development stage has just been divided into two phases (early and late), followed by the commercialisation stage after marketing authorisation. The aim of Table 1 is to document that disciplinary knowledge is also very important in the drug development process and that different disciplines contribute to different stages of the drug life cycle. Combined studies are not indicated in Table 1, but can be quite valuable, for example, a primary degree in Pharmaceutical Sciences and a second degree in Patent Law.
\nAs can be seen in Table 1, the most important academic knowledge base is contributed by PhD holders in the various molecular, biotech and life sciences during stages 1 and 2, which are focused on drug discovery and non-clinical development. Academics with a background in the pharmaceutical and medical sciences can typically use their knowledge base during the whole drug life cycle. For the more advanced stages in the life cycle, a PhD could still be an advantage, but the valorisation of academic knowledge developed during the PhD studies will likely become less important, while the transferable skills and behaviours of PhD holders will start to predominate. This also implies that a vast range of academics listed in Table 1, can professionally contribute to any of the stages of the drug life cycle. The fact that crosses are lacking in certain positions merely indicates that in those positions the original academic knowledge base is unlikely to be the main contributor to the activities in that stage. Thus, a biologist that is employed as a Clinical Research Associate (CRA) and active in the later stage of clinical development will not have a cross in this part of Table 1 (because there is no dominance of biological key knowledge in that stage), but he/she can still build out a very interesting career. Table 1 is not based on quantitative data but rather reflects the authors’ views on where specific academic disciplinary knowledge is expected to be most valuable in the drug life cycle.
\nSuccessful job application requires three things: (1) having a good motivation, (2) having the required technical skill set and (3) being able to illustrate your interpersonal skills.
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The cover letter functions to express motivation and qualifications for the job.
It is important to be concise and not too long (not more than one A4-page).
Make an overview of the required hard and soft skills of the job advertisement.
As a recent graduate you may not have all the required skills. You can still apply when covering 70–80% of all skills required.
Make sure that the cover letter mentions all the hard and soft skills that you have.
Use as much as possible the labels that are used in the job advertisement.
With regard to the soft skills: describe a few activities in your current work or projects that illustrate your roles and results.
Make clear what is important to you in your work (your professional goals) and how this links to the job content and the goals of the organization.
Highlight those qualifications that make you an outstanding candidate.
Use strong wording (not I think or I believe) and don’t make interpretations for the jury.
Again employers look for motivation and skills, make sure that you illustrate both in your CV.
The work experience section is most important, describe all your roles and quantify the results. Also include relevant extracurricular activities and internships.
You may include your motivation by adding a short elevator pitch (
Your CV should be in line with your LinkedIn profile and other open sources available on the Internet with regard to your profile (Twitter, Facebook, Research gate, etc.).
Be short and concise (max. two A4-pages).
The purpose of a job interview is to sell yourself and receive a job offer.
A job interview starts with introducing yourself: prepare an elevator pitch.
With regard to motivation: formulate what you can add to the organisation, not what is in it for yourself.
Your body language is very important. Talk slowly, look into the eyes of all the jury members, give a firm handshake and have a confident look.
Stay cool during a job interview; do not get irritated, even if the jury asks you confronting questions.
Prepare three examples of your biggest achievements in your work, studies, or extracurricular activities that you can use to illustrate your skills. Describe the context, your role, the activities that you initiated and the results.
Make sure that you can reflect on your results. Employers love employees who are open for criticism and want to improve continuously.
Prepare three positive sides and three negative sides. Explain how you cope with your downsides.
Many tricky questions are another way of checking again on your motivation and qualifications for the job. Just repeat what you have been saying in a nice way.
Never discuss money or benefits before you are offered a job.
Our writing of this chapter is based on the notion that a successful launch of a career in the pharmaceutical sector depends on an overall knowledge of this sector and on a smart strategy for job application. Besides these two key elements, many companies recruit via their traineeship programs as discussed in Section 7. One should realise that also in this sector, the vast majority of jobs are never advertised. For this reason, training and networking is indeed a far more effective job-seeking strategy than screening magazines and websites for advertisements. This partly hidden job market also implies that the first step from academia to the pharmaceutical sector is often experienced as the hardest and most important one; it will determine your direction and your differentiation as an employee. At the same time, you will access a new network of professionals with its own word-of-mouth that can become vital for your next career moves.
\nBesides all the aspects already treated in this chapter, there are only a few closing remarks left, worth to take into account. Jobs in the pharmaceutical sector often come in location-related clusters in Europe. These so-called research parks are often located near international research-oriented universities, where graduates are directly available for recruitment purposes. When new centres are opened, often several jobs are available, even if you can only apply for one at the time. One should realise that these new centres could only become successful when the vacancies are rapidly filled and the industrial annual targets are reached in that specific location. If vacancies stay open too long, the company will most likely move to another location. This implies that research and development hot spots in, for example, Europe can compete with each other through the speed they reach in filling their vacancies and grow more successful as a site. For this reason, it is very important for academic graduates with the right qualifications to be willing to move to a new national or international location, to fill that vacancy that perfectly matches their particular hard and soft skills and become employed in a larger R&D hotspot that might also offer perspectives for additional career moves in the future. It requires some additional study and networking to become aware of the upcoming hotspots relevant for your particular area of interest.
\nA last reflection is about the important work versus private life balance. If you talk to successful people in the pharmaceutical sector, you will often quickly discover that they really love their job and that, as a consequence, they work a lot. This does not mean that they have squeezed their family life to a minimum, but there are positions in this sector that simply demand more than just the regular office hours. Companies may differ in their philosophies about the work-life and gender balance and it can be an advantage to know their general view about this.
\nFurther improvement of human health largely depends on the development of new methods in prevention, early diagnosis and treatment of disease. An input of new knowledge from young employees with fresh inspiration and energy to achieve this goal is vital for the pharmaceutical sector. With this chapter, we hope to have opened the door and lowered the threshold to enter an exciting world of opportunities.
\nPhotosynthetic eukaryotic organisms harbor a chloroplast genome (also called ‘plastome’) within their cells. This genome derives from the endosymbiosis of a prokaryotic organism, which was then gradually converted into the chloroplast. With the increased number of sequences within publicly available databases and the emergence of very sophisticated phylogenetic and phylogenomic analyses, we can infer much more precisely the origin of this primary endosymbiotic event. In addition, these comparative analyses allow for investigation of plastome evolutionary dynamics in the different plant lineages and the extent of nuclear influence over the chloroplast genome. Overall, plant plastomes harbor a very low gene content compared to their prokaryotic ancestor, which appears to result from either gene loss due to redundant functions in both chloroplast and nuclear genomes or functional transfer and relocation of chloroplast genes into the nucleus. The relocation of thousands of chloroplast genes from the chloroplast to the nucleus was rendered possible due to the massive transfer of DNA from the chloroplast to the nucleus. However, chloroplast genes that have been integrated into the nucleus are not immediately functional and have to adapt to their new eukaryotic environment by acquiring various regulatory elements (i.e., promoter, polyadenylation signal, and target peptide). Despite most of these functional transfers occurred soon after the endosymbiotic event, some clever real-time experiments (using a selectable marker) have allowed for understanding how easily and by which molecular mechanisms DNA is transferred from the chloroplast to the nucleus. Such experiments have also permitted the study of the subsequent evolution of chloroplast DNA in the nuclear genome, and how a chloroplast gene becomes functional in the nucleus.
Photosynthetic eukaryotic cells arose through the engulfment of a cyanobacterium that was then converted into the chloroplast, enabling plants to use sunlight to fix carbon. This major functional innovation allowed for eukaryotes to transition from heterotrophy to autotrophy. This primary endosymbiotic event is at the origin of the astonishing biodiversity visible today in plants, including the Glaucophyta, Rhodophyta, and Viridiplantae lineages (Figure 1). With the advent of next-generation sequencing technologies, the number of fully sequenced plastomes has hugely expanded, providing insight into chloroplast evolution in the different plant lineages. In this part, we will present our current knowledge on chloroplast origin and what has been unraveled on the chloroplast genome evolution, regarding genome size, gene content, structure, and mutation rate.
Phylogenetic relationships of the different plant lineages formed after the primary endosymbiosis of a cyanobacterium by an ancestor of the Archaeplastida. The number of available genomes on GenBank is indicated under the image. For simplicity, “Mosses, Marchantyophytes and Bryophytes” on one side, as well as “Ferns and Lycopodiophyta” on the other side, were grouped together in the tree. Pictures copyright to L. Brient, M.T. Misset, R. Delourme, and J. Keller.
The first hypothesis of the endosymbiotic origin of chloroplasts is commonly credited to Russian botanist K. Mereschkowsky, who observed similarities between cyanobacteria and chloroplasts of plants and algae [1]. This hypothesis was then reaffirmed by Margulis in the 1970s. The origin of this primary endosymbiosis event is still debated. While fossil-based phylogeny estimated the origin of chloroplasts to be around 1.4–1.7 billion years ago [2], gene-based approaches dated it around 0.9 billion years ago [3]. Different phylogenetic analyses aimed at determining the cyanobacterial lineage from which the chloroplast was derived and revealed that chloroplasts were closely related to the nitrogen-fixing cyanobacteria Chroococcales,
It is now widely accepted that this primary endosymbiotic event has a single origin [6, 7, 8]; however, it is still unclear how long it took for the conversion of the bacterial endosymbiont into a fully integrated organelle. This transition from endosymbiont to organelle surely involved many steps. The first steps corresponded to the loss of the bacterial wall and the early acquisition by the endosymbiont of a transport system to transfer proteins and metabolites from the cytosol to the chloroplast. This latter step is constituted by two protein complexes: translocon of the outer (TOC) membranes of the chloroplast and translocon of the inner (TIC) membranes of the chloroplast [9, 10, 11]. The TIC/TOC complexes allow for transportation of the pre-proteins (proteins with a cleavable chloroplast target peptide) from the cytosol, where they are synthetized, to the chloroplast, where the target peptide is cleaved (reviewed in [11]). The presence of the same protein import apparatus in the different Archaeplastida lineages is the best evidence of the single origin of chloroplasts. Finally, the transition also necessitated the gradual functional transfer of endosymbiont genes to the nucleus [12], leading to the massive reduction of plastome size and gene content.
Most of our current knowledge of the conversion from endosymbiont to organelle has been obtained by comparing contemporary Archaeplastida organelles with their closest bacterial relatives. During the last few years, advances in high-throughput sequencing and bioinformatic methods greatly facilitated the assembly, analysis, and publication of complete plastomes. To date, more than 2300 plastomes are fully assembled and deposited in the GenBank database. This number of plastomes actually doubled in the last 2 years. However, the number of sequenced plastomes varies greatly between the different Archaeplastida lineages. Indeed, almost 80% of them belong to Angiosperms. Thus, there is an important inequality in the sequencing effort. The poor level of plastome sequencing in plant lineages outside of the Angiosperms needs to be improved to fully understand chloroplast genome evolution in plants. Some efforts to fill this gap have been performed in the last 2–5 years, but they are still insufficient. In the Glaucophyta, only one chloroplast genome is available (NC_001675), and another is sequenced but not yet published (Lang et al., unpublished). In contrast, the sequencing of Rhodophyta and Chlorophyta (green algae
Cumulative numbers of full chloroplast genomes deposited in GenBank for (A) Rhodophyta, (B) Chlorophyta, and (C) Streptophyta.
As mentioned previously, the conversion of the cyanobacterial endosymbiont into a chloroplast necessitated the functional transfer or replacement of most cyanobacterial genes into the nucleus. Compared to the thousands of genes (at least 2000) thought to have been once present in the cyanobacterial genome, Archaeplastida plastomes encode a maximum of around 250 genes [13, 14]. This observation indicates that most genes (includes protein coding and structural RNAs) present in the cyanobacterial ancestor have been functionally transferred relatively soon after the endosymbiotic event. Despite gene content among modern chloroplast genomes being relatively well conserved, there are important variations. Thus, Rhodophyta have the highest number of genes (237 in average; minimum 207; up to 266 in
Plastome numbers and characteristics (average size, number of proteins, and structural RNAs) among the Archaeplastida. The minimum and maximum genome sizes are indicated in italic.
These variations in gene content revealed the divergent evolution of plastomes in the different lineages. As an example, Rhodophyta gene content is characterized by the complete absence of the NADPH dehydrogenase complex [15]. Conversely, some genes are Rhodophyta-specific or rare in other Archaeplastida such as RNase P RNA, tmRNA, or signal recognition particle RNA [16, 17, 18]. Rhodophyta chloroplasts generally have a large genome size (see later) characterized by a high number of genes and other features such as the presence of bacteria-like operons, suggesting that Rhodophyta plastomes are phylogenetically closest to the ancestral cyanobacteria genome than any other algae [15]. Gene content variations are also well documented in the Angiosperm family in which multiple independent gene losses have been found such as
Among plants, chloroplast genomes range from less than 100 kb to more than 1 Gb, again excluding the non-chlorophyll species that exhibit significantly smaller chloroplast genomes (Table 1). The largest chloroplast genome ever sequenced has very recently been found in the red algae
Several factors can explain the important size variations found among the Archaeplastida. In the case of the red algae
Among plants, most plastomes seem to exhibit a conserved quadripartite structure, with a large and small single copy separated by two inverted repeats (Palmer 1983). However, multiple rearrangements occurred in diverse lineages, which modified this conserved structure. One of the most striking examples is the loss of one IR that occurred multiple times in the different chloroplast-bearing lineages, such as in the Fabaceae and the Geraniaceae [30, 33, 34]. This has also been reported for different Gymnosperms species such as
Chloroplast genome structure and gene order are also highly affected by inversions. Many inversions have been described in the literature, especially in legumes, with, for instance, fragments of 50 kb in the Papilionoideae [38], 36 kb in the Genistoids [39]; 29 kb in Sophoreae [40] or 7 kb in
Chloroplast genomes are known to be highly conserved, with relatively low rates of mutations, especially when compared to the plant nuclear genome. Indeed, the chloroplast genome evolves on average 10 times slower than the nuclear genome [45], with about 1 or less mutation/kb/million years [46] compared with approximately 7 mutations/kb/million years for the nuclear genome [47]. However, there are some exceptions, especially in three Angiosperm families (i.e., Fabaceae, Campanulaceae, and Geraniaceae) that are known to have accelerated evolutionary rates of their plastomes along with multiple structural rearrangements and size variations [19, 28, 30, 42, 44, 48, 49]. For example, the
To sum up this first section on the origin and evolution of plant plastomes originating from the primary endosymbiosis event, the recent sequencing and bioinformatics progress significantly increased the number of chloroplast genomes available for the scientific community. These advances have greatly improved our knowledge about the evolutionary dynamics of plastomes. Despite the diversity of organisms that harbor chloroplasts, plastomes in general seem to be relatively well conserved among the Archaeplastida (in terms of structure, size, and gene content); however, multiple independent alterations of these features have been observed in the different lineages. In addition, a few plant families (or group of species) seem to present an atypical evolution of the chloroplast genome. It is certain that the continuous effort to sequence much more plastomes (especially in the Glaucophyta and Rhodophyta) will allow the identification of new examples of such atypical evolution and will permit a better understanding of what are the causes and the molecular mechanisms involved in limiting or increasing plastome evolution.
Since the endosymbiotic event, the host genome (nuclear) has acquired most of the cyanobacterial genes, leading to the gradual loss of autonomy of the endosymbiont and the reduction of its genome. In this part, we will present our current knowledge on the mechanisms as well as the numerous cases of chloroplast DNA transfers to the nucleus and where it is now integrated in the nuclear genome. We will then detail the subsequent evolution and adaptation processes of the chloroplast genome that took place in its new eukaryotic environment. We will also discuss which factors can influence relocation of a chloroplast gene to the nucleus, and how a chloroplast gene transferred to the nucleus may become functional. Finally, we will discuss the important role that transfer of chloroplast DNA to the nucleus plays in the process of diversifying the plant nuclear gene content.
Much earlier than the complete sequencing and assembly of the first chloroplast genome (
Some of the chloroplast DNA fragments that were experimentally shown to insert in the nuclear genome were characterized [55, 60] and were often large in size (usually greater than 10 kb in length). Considering the massive transfer of chloroplast DNA to the nucleus, one would expect that some of these
Following endosymbiosis, the symbiont to organelle transition involved many steps. This includes the loss of the bacterial cell wall, the acquisition of a protein machinery that transfers nuclear-encoded proteins from the cytosol to the chloroplast (also known as the TIC and TOC complexes [75, 76]), and finally, the functional relocation of most chloroplast genes to the nucleus. As detailed below, a chloroplast gene may be replaced either only after its functional transfer to the nucleus, or directly substituted by a gene of a mitochondrial or eukaryotic origin.
Since the endosymbiosis event, thousands of genes have relocated within the nuclear genome. Indeed, cyanobacterial genomes encode a minimum of 2000 proteins, whereas current plant plastomes encode only 80–200 proteins, although 800 to more than 2000 proteins have been found in some algae and plant chloroplasts [77], respectively. Apart from some genes that presented redundant functions in both chloroplast and nuclear genomes, most chloroplast genes have been functionally relocated to the nucleus with their proteins targeted back to the organelle. Thus, the spectrum of proteins required for function and biogenesis of the cytoplasmic organelle did not greatly evolve since its creation.
The current plastome of most plants encodes a maximum of 200 proteins [78] whereas more than 2000 proteins in the chloroplast, suggesting the functional gene transfer and relocation of most chloroplast genes to the nucleus. As chloroplast genes are of prokaryote origin, they are not readily functional in the nuclear genome. To function in this novel environment, a chloroplast gene has to acquire or hijack nuclear gene regulatory elements (eukaryote promoter and terminator), as well as a transit peptide to target the protein back to the chloroplast [60, 79]. However, the acquisition of all these nuclear elements does not have to take place right after the transfer of the chloroplast gene to the nucleus, as they can retain their open reading frames for several million years [71]. In addition, some chloroplast genes can be relatively easily functional as a few chloroplast promoters (i.e.,
To date, the number of chloroplast-encoded proteins (about 80) is relatively well conserved among flowering plants. However, a few chloroplast genes have been independently lost in various plant lineages [19], allowing to understand how they became functional. Such chloroplast gene losses were most particularly observed in the Fabaceae, for which the plastome has been extensively reorganized and contains localized accelerated mutation rates [19]. Some of these genes, such as
The functional replacement of a chloroplast gene does not necessarily necessitate its functional transfer from the chloroplast to the nucleus. In the case of the chloroplast RPS16 protein, the chloroplast
Another evolutionary mechanism enabling the functional replacement of a chloroplast gene may occur
The continuous deluge of organellar DNA to the nucleus has facilitated the functional transfer of almost all chloroplast genes to the nucleus, reducing extensively the plastome size. Additionally, this organellar DNA was not only used to replace organellar genes but also enabled diversifying the plant nuclear gene content [77].
Chloroplast gene sequences transferred to the nucleus may present different fates. As presented in the two previous sections: (i) they may remain non-functional, decay, and ultimately be lost; (ii) they may acquire all the necessary elements to conserve the same function and have the protein targeted back to the chloroplast; or (iii) they may acquire new subcellular locations and functions. As mentioned earlier, Martin
The conversion of the cyanobacterial endosymbiont into the chloroplast partly results from the gradual transfer of hundreds to thousands of endosymbiont genes to the nuclear host. Across all lineages, more than 90% of the plant chloroplast proteins are now encoded in the nucleus. Within the few chloroplast-encoded proteins, about 40% of them are involved in chloroplast protein complexes that are made up of proteins encoded in both the chloroplast and the nucleus. These complexes exhibit important functions that are vital for the plant, such as photosystems I and II. One can only wonder how the stoichiometry between those two compartments is maintained. Indeed, one cell might contain hundreds to thousands of chloroplast copies compared to only one copy in the nucleus. Furthermore, chloroplast inheritance is often maternal, whereas nuclear bi-parental inheritance occurs in angiosperms during sexual reproduction. Therefore, coevolving interactions between cytoplasmic and nuclear genomes have been necessary and have resulted in significant coadaptation processes. When these fine-tuned coevolutionary interactions are disrupted, after intra-interspecific hybridization and/or genome doubling, for instance, incompatibilities and deleterious phenotypes can be observed. These evolutionary processes will be discussed in the light of previous work on synthetic and natural hybrids, as well as in polyploid species.
Several evolutionary scenarios can explain coadaptation between chloroplast and nuclear genomes after intraspecific hybridization. First, cytoplasmic genomes lack sexual reproduction and are more susceptible to fix and accumulate deleterious mutations by genetic drift [93]. Only positive selection for compensatory nuclear alleles will allow for regaining of optimal organelle function [94]. This mechanism of
Second, some mutations in the organelles could also be adaptive in specific environments and fixed in the population by natural selection. Subsequently, coadaptation process may favor specific nuclear variants to preserve intergenomic interactions. This mechanism is called
As mentioned above, the examples for intergenomic coadaptation and incompatibilities are scarce, and we are still very far from unraveling the molecular processes underlying such interactions. Applications of genome-wide studies in association with high-throughput sequencing would greatly improve our understanding of cytonuclear coevolution.
As shown above, cytonuclear interactions are extremely fine-tuned coevolved molecular processes that are still largely understudied. However, in recent years, efforts have been made, especially in neo-polyploid plant species (natural and resynthesized) to better apprehend the consequences of whole genome duplication (WGD) and interspecific hybridization on cytonuclear interactions and stability. In this last section, we will review our knowledge on such systems and elaborate on the many future issues to address.
Although completely overlooked, it is astonishing to envision the numerous and drastic consequences of a WGD event on copy number variation and stoichiometry on those cytonuclear complexes. Impacts of WGD on genomic structure and functional changes have been extensively studied in a large variety of plant systems. Genome redundancy can lead to changes in epigenetic patterns (including transposable element dynamics), altered gene expression (changes in global gene expression but also possible biased contribution of redundant copies), and fractionation processes (gene loss, homologous and non-homologous exchanges). However, to date, very few studies have investigated how the duplication of nuclear genes would affect the assembly dynamics of the multi-subunit cytonuclear complexes [103]. Different hypotheses predict the fate of nuclear and cytoplasmic genes implicated in cytonuclear complexes. They are based on the prediction that selection will favor compensatory mechanisms to maintain coordinated expression between cytoplasmic and nuclear genes leading
Only a handful of studies have looked at the consequences of WGD on a longer time scale, in that case, occurrences of subfunctionalization and pseudogenization of duplicated copies are to be expected. Coate et al. [109] stated that there might be a considerable influence of cytonuclear complex sensitivity to gene dosage imbalance and thus the need to return to single copy status or stay in duplicates. More specifically, Coate et al. [109] demonstrated that in
All of these processes could be enhanced through allopolyploidy, where divergent parental species first hybridized before genome doubling. In that case, the nuclear genome is redundant and a mixture of two, more or less, divergent parental genomes, whereas the organelles have (usually) a uniparental origin. Therefore, as chloroplast inheritance is usually maternal, selection should favor maintenance of maternal nuclear copies over the paternally inherited homoeolog as to preserve pre-existing coadaptive cytonuclear interactions. In allopolyploids, different scenarios leading to pseudogenization of paternal copies can be envisioned and were tested in a limited set of genes and species. The first scenario involves downregulation and relaxed selection of the paternally inherited homoeolog. An alternative scenario involves preferential gene conversion to the maternal homoeolog resulting in the loss of the paternal-like copy. It is important to note that both scenarios are not exclusive but could be part of a dynamic and gradual process, with first overexpression of the maternal copies leading to paternal homoeolog pseudogenization and maternally biased gene conversion. These hypotheses have only been tested in the Rubisco nuclear-encoded gene
These few studies already highlight the complexity of the different model systems that can be highly influenced by various evolutionary processes such as pre-existing coadaptive mechanisms, natural selection, and divergence between parental individuals (different populations to different species). As all Angiosperms have experienced at least one round of genome duplication and most of them multiple WGDs (Triticum and Brassica), paleopolyploid species are perfect candidates to elucidate the long-term impact of diploidization and biased genome fractionation on rates of asymmetric gene loss and pseudogenization. Additionally, it seems essential to integrate plant families that have contrasted rate of chloroplastic evolution (such as in Geraniaceae, Campanulaceae, and Fabaceae) and paternally inherited chloroplast genomes (such as in Actinidia, Medicago, and most Conifers). Finally, life history features such as reproductive strategy (perennial vs. annual), mating system (selfer vs. outcrosser), population level dynamics, and effective population size will also impact fixation rate of mutations.
We would like to thank the European Union Seventh Framework Program (FP7-CIG-2013-2017; Grant No. 333709 to Mathieu Rousseau-Gueutin) and an Agreenskills Plus fellowship to Julie Ferreira de Carvalho. We would also like to thank Dr. Christina Richards (Department of Integrative Biology, University of South Florida) for carefully and critical reading of the manuscript.
No conflict of interest.
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. Aalborg University has Two Satellite Campuses, one in Copenhagen (Aalborg University Copenhagen) and the other in Esbjerg (Aalborg University Esbjerg).\n· He is a member of prestigious IEEE (Institute of Electrical and Electronics Engineers), and IAENG (International Association of Engineers) organizations. \n· He is the chief Editor of the Journal of Software Engineering.\n· He is the member of the Editorial Board of International Journal of Computer Science and Software Technology (IJCSST) and International Journal of Computer Engineering and Information Technology. \n· He is also the Editor of Communication in Computer and Information Science CCIS-20 by Springer.\n· Reviewer For Many Conferences\nHe is the lead person in making collaboration agreements between Aalborg University and many universities of Pakistan, for which the MOU’s (Memorandum of Understanding) have been signed.\nProfessor Akbar is working in Academia since 1990, he started his career as a Lab demonstrator/TA at the University of Sussex. After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. He has contributed in stochastic estimation of control area especially, in the Multiple Target Tracking and Interactive Multiple Model (IMM) research, Ball & Beam Control Problem, Robotics, Levitation Control. He has contributed in developing Algorithms for Fingerprint Matching, Computer Vision and Face Recognition. He has been supervising Pattern Recognition, Formal Languages and Distributed Processing projects for several years. He has reviewed many books on Management, Computer Science. Currently, he is an active and permanent reviewer for many international conferences and symposia and the program committee member for many international conferences.\nIn teaching he has taught the core computer science subjects like, Digital Design, Real Time Embedded System Programming, Operating Systems, Software Engineering, Data Structures, Databases, Compiler Construction. In the Engineering side, Digital Signal Processing, Computer Architecture, Electronics Devices, Digital Filtering and Engineering Management.\nApart from his Academic Interest and activities he loves sport especially, Cricket, Football, Snooker and Squash. He plays cricket for Esbjerg city in the second division team as an opener wicket keeper batsman. 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The chapter is focused on the bimodal actions of ROS, which can be summarized as both beneficial and negative. The beneficial aspects of ROS are related to their effects on the redox state of cells and the important role that some ROS play in signaling cascade. The detrimental effects of ROS are related excess amounts of these chemical moieties, which are caused by excessive production and/or insufficient actions of endogenous antioxidants. The generation of these species is also discussed.",book:{id:"6333",slug:"reactive-oxygen-species-ros-in-living-cells",title:"Reactive Oxygen Species (ROS) in Living Cells",fullTitle:"Reactive Oxygen Species (ROS) in Living Cells"},signatures:"Roma Patel, Lindsey Rinker, Joanna Peng and William M. Chilian",authors:[{id:"192680",title:"Dr.",name:"Wiliam M.",middleName:null,surname:"Chilian",slug:"wiliam-m.-chilian",fullName:"Wiliam M. Chilian"},{id:"212032",title:"Ms.",name:"Lindsey",middleName:null,surname:"Rinker",slug:"lindsey-rinker",fullName:"Lindsey Rinker"},{id:"212033",title:"Ms.",name:"Roma",middleName:null,surname:"Patel",slug:"roma-patel",fullName:"Roma Patel"},{id:"212034",title:"Ms.",name:"Joanna",middleName:null,surname:"Peng",slug:"joanna-peng",fullName:"Joanna Peng"}]},{id:"58369",doi:"10.5772/intechopen.72747",title:"Reactive Oxygen Species in Skin Repair, Regeneration, Aging, and Inflammation",slug:"reactive-oxygen-species-in-skin-repair-regeneration-aging-and-inflammation",totalDownloads:2101,totalCrossrefCites:15,totalDimensionsCites:29,abstract:"As the most important and largest surface barrier, the skin provides a necessary protection to the organism from the external factors, including chemical, biological, and physical irritation, injury, and others. External environmental irritants or their metabolites are inherent oxidants and/or directly or indirectly drive the production of various reactive oxidants, reactive oxygen species (ROSs), owing to the redox imbalances. ROSs, the most common free oxygen radicals, participate in a series of physiological and pathological skin processes. Here, we discussed the role of oxidative events in injury, repair, photoaging, and cutaneous disease development. Intrinsic and extrinsic factors lead to the skin barrier damage, which leads to the disequilibrium in oxidant and antioxidant balance and induces excessive ROS production. The underlying mechanisms include DNA damage, MAPK/AP-1, NF-κB, and JAK/STAT-signaling pathways, apoptosis and autophagy, and autoimmune reaction of melanocytes and keratinocytes. The skin employs a number of antioxidant agents to protect the oxidative balance, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), ascorbic acid, and tocopherols. The results presented here indicate that antioxidant treatments may be effective when applied in the therapy of cutaneous diseases where oxidative stress plays a prominent pathogenic role.",book:{id:"6333",slug:"reactive-oxygen-species-ros-in-living-cells",title:"Reactive Oxygen Species (ROS) in Living Cells",fullTitle:"Reactive Oxygen Species (ROS) in Living Cells"},signatures:"Hui Xu, Yun-Wen Zheng, Qi Liu, Li-Ping Liu, Feng-Lin Luo, Hu-Chen\nZhou, Hiroko Isoda, Nobuhiro Ohkohchi and Yu-Mei Li",authors:[{id:"63284",title:"Prof.",name:"Nobuhiro",middleName:null,surname:"Ohkohchi",slug:"nobuhiro-ohkohchi",fullName:"Nobuhiro Ohkohchi"},{id:"216569",title:"Associate Prof.",name:"Yun-Wen",middleName:null,surname:"Zheng",slug:"yun-wen-zheng",fullName:"Yun-Wen Zheng"},{id:"216572",title:"Dr.",name:"Hui",middleName:null,surname:"Xu",slug:"hui-xu",fullName:"Hui Xu"},{id:"216574",title:"Dr.",name:"Qi",middleName:null,surname:"Liu",slug:"qi-liu",fullName:"Qi Liu"},{id:"216576",title:"Dr.",name:"Yu-Mei",middleName:null,surname:"Li",slug:"yu-mei-li",fullName:"Yu-Mei Li"},{id:"234877",title:"BSc.",name:"Feng-Lin",middleName:null,surname:"Luo",slug:"feng-lin-luo",fullName:"Feng-Lin Luo"},{id:"234878",title:"BSc.",name:"Zhou",middleName:null,surname:"Hu-Chen",slug:"zhou-hu-chen",fullName:"Zhou Hu-Chen"},{id:"234880",title:"Prof.",name:"Hiroko",middleName:null,surname:"Isoda",slug:"hiroko-isoda",fullName:"Hiroko Isoda"},{id:"234884",title:"Dr.",name:"Li-Ping",middleName:null,surname:"Liu",slug:"li-ping-liu",fullName:"Li-Ping Liu"}]},{id:"34558",doi:"10.5772/35847",title:"The Epididymis: Embryology, Structure, Function and Its Role in Fertilization and Infertility",slug:"the-epididymis-embryology-structure-function-and-its-role-in-fertilization-and-infertility",totalDownloads:13361,totalCrossrefCites:9,totalDimensionsCites:21,abstract:null,book:{id:"1699",slug:"embryology-updates-and-highlights-on-classic-topics",title:"Embryology",fullTitle:"Embryology - Updates and Highlights on Classic Topics"},signatures:"Kélen Fabiola Arrotéia, Patrick Vianna Garcia, Mainara Ferreira Barbieri, Marilia Lopes Justino and Luís Antonio Violin Pereira",authors:[{id:"106080",title:"Prof.",name:"Luis",middleName:"Antonio",surname:"Violin Pereira",slug:"luis-violin-pereira",fullName:"Luis Violin Pereira"},{id:"112722",title:"Dr.",name:"Kélen",middleName:null,surname:"Arrotéia",slug:"kelen-arroteia",fullName:"Kélen Arrotéia"},{id:"112724",title:"MSc.",name:"Patrick",middleName:null,surname:"Garcia",slug:"patrick-garcia",fullName:"Patrick Garcia"},{id:"112726",title:"BSc.",name:"Mainara",middleName:null,surname:"Barbieri",slug:"mainara-barbieri",fullName:"Mainara Barbieri"},{id:"112727",title:"BSc.",name:"Marília",middleName:null,surname:"Justino",slug:"marilia-justino",fullName:"Marília Justino"}]},{id:"58039",doi:"10.5772/intechopen.72217",title:"Role of Antioxidant Phytochemicals in Prevention, Formation and Treatment of Cancer",slug:"role-of-antioxidant-phytochemicals-in-prevention-formation-and-treatment-of-cancer",totalDownloads:1687,totalCrossrefCites:8,totalDimensionsCites:17,abstract:"Reactive oxygen species (ROS) played an important role in cancer. Although low levels of ROS can be beneficial in normal physiological functions, chronic exposure to ROS is associated with increased risk of cancers. Increased ROS levels can also induce apoptosis and cell death in various types of cancer. Taken together, the role of ROS in cancer prevention, formation and therapy is extremely complex and very challenging to study. Although the antioxidant activity of phytochemicals is well recognized and generally used to prevent cancer, they can have pro-oxidant and ROS generating activities under certain conditions, especially at high doses or in the presence of metal ions. The basal redox levels of cancer cells are also different from those of normal cells. Therefore, higher levels of free form of metal ions and higher levels of endogenous ROS production in cancer cells sensitizes them to phytochemicals mediated pro-oxidant cytotoxicity. In conclusion, people tend to intake of antioxidant phytochemicals for the detrimental effects of ROS. However, excessive intake of phytochemicals could have cancer development or therapeutic potential by generating ROS. In this section, the role of phytochemicals in the prevention, development and removal of cancer has been discussed.",book:{id:"6333",slug:"reactive-oxygen-species-ros-in-living-cells",title:"Reactive Oxygen Species (ROS) in Living Cells",fullTitle:"Reactive Oxygen Species (ROS) in Living Cells"},signatures:"Abdurrahim Kocyigit, Eray Metin Guler and Murat Dikilitas",authors:[{id:"87750",title:"Dr.",name:"Murat",middleName:null,surname:"Dikilitas",slug:"murat-dikilitas",fullName:"Murat Dikilitas"},{id:"213091",title:"Prof.",name:"Abdurrahim",middleName:null,surname:"Koçyiğit",slug:"abdurrahim-kocyigit",fullName:"Abdurrahim Koçyiğit"},{id:"223224",title:"Dr.",name:"Eray Metin",middleName:null,surname:"Guler",slug:"eray-metin-guler",fullName:"Eray Metin Guler"}]},{id:"62993",doi:"10.5772/intechopen.80056",title:"Role of Apoptosis in Cancer Resistance to Chemotherapy",slug:"role-of-apoptosis-in-cancer-resistance-to-chemotherapy",totalDownloads:1811,totalCrossrefCites:9,totalDimensionsCites:16,abstract:"Cancer is a leading cause of death in human beings. Surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy are common modalities for cancer treatment. However, cancer resistance is common in chemotherapy and often leads to therapeutic failure. This chapter addresses the role of apoptosis in tumor’s resistance to chemotherapy and the underlying mechanisms. Cancer cells are always resistant to apoptotic signals via a series of biochemical changes. Cancer cells are resistant to chemotherapeutic agents that are potent apoptosis inducers via multiple mechanisms, such as upregulated anti-apoptotic signals and downregulated pro-apoptotic signals, faulty apoptotic signaling, faulty apoptosis initiation and implementation, etc. We also discuss the possible approaches to overcoming cancer resistance to chemotherapy due to altered apoptosis.",book:{id:"6618",slug:"current-understanding-of-apoptosis-programmed-cell-death",title:"Current Understanding of Apoptosis",fullTitle:"Current Understanding of Apoptosis - Programmed Cell Death"},signatures:"Lichan Chen, Yanyun Zeng and Shu-Feng Zhou",authors:[{id:"229027",title:"Prof.",name:"Shu-Feng",middleName:null,surname:"Zhou",slug:"shu-feng-zhou",fullName:"Shu-Feng Zhou"}]}],mostDownloadedChaptersLast30Days:[{id:"18220",title:"How do Mesenchymal Stem Cells Repair?",slug:"how-do-mesenchymal-stem-cells-repair-",totalDownloads:6051,totalCrossrefCites:9,totalDimensionsCites:16,abstract:null,book:{id:"216",slug:"stem-cells-in-clinic-and-research",title:"Stem Cells in Clinic and Research",fullTitle:"Stem Cells in Clinic and Research"},signatures:"Patricia Semedo, Marina Burgos-Silva, Cassiano Donizetti-Oliveira and Niels Olsen Saraiva Camara",authors:[{id:"28751",title:"Prof.",name:"Niels",middleName:"Olsen Saraiva",surname:"Camara",slug:"niels-camara",fullName:"Niels Camara"},{id:"30464",title:"Prof.",name:"Patricia",middleName:null,surname:"Semedo",slug:"patricia-semedo",fullName:"Patricia Semedo"},{id:"30465",title:"BSc.",name:"Cassiano",middleName:null,surname:"Donizetti-Oliveira",slug:"cassiano-donizetti-oliveira",fullName:"Cassiano Donizetti-Oliveira"},{id:"30466",title:"BSc.",name:"Marina",middleName:null,surname:"Burgos-Silva",slug:"marina-burgos-silva",fullName:"Marina Burgos-Silva"}]},{id:"57536",title:"Reactive Oxygen Species: The Good and the Bad",slug:"reactive-oxygen-species-the-good-and-the-bad",totalDownloads:3607,totalCrossrefCites:23,totalDimensionsCites:42,abstract:"This chapter summarizes recent research on the biology of reactive oxygen species (ROS). The chapter is focused on the bimodal actions of ROS, which can be summarized as both beneficial and negative. The beneficial aspects of ROS are related to their effects on the redox state of cells and the important role that some ROS play in signaling cascade. The detrimental effects of ROS are related excess amounts of these chemical moieties, which are caused by excessive production and/or insufficient actions of endogenous antioxidants. The generation of these species is also discussed.",book:{id:"6333",slug:"reactive-oxygen-species-ros-in-living-cells",title:"Reactive Oxygen Species (ROS) in Living Cells",fullTitle:"Reactive Oxygen Species (ROS) in Living Cells"},signatures:"Roma Patel, Lindsey Rinker, Joanna Peng and William M. Chilian",authors:[{id:"192680",title:"Dr.",name:"Wiliam M.",middleName:null,surname:"Chilian",slug:"wiliam-m.-chilian",fullName:"Wiliam M. Chilian"},{id:"212032",title:"Ms.",name:"Lindsey",middleName:null,surname:"Rinker",slug:"lindsey-rinker",fullName:"Lindsey Rinker"},{id:"212033",title:"Ms.",name:"Roma",middleName:null,surname:"Patel",slug:"roma-patel",fullName:"Roma Patel"},{id:"212034",title:"Ms.",name:"Joanna",middleName:null,surname:"Peng",slug:"joanna-peng",fullName:"Joanna Peng"}]},{id:"62993",title:"Role of Apoptosis in Cancer Resistance to Chemotherapy",slug:"role-of-apoptosis-in-cancer-resistance-to-chemotherapy",totalDownloads:1811,totalCrossrefCites:9,totalDimensionsCites:16,abstract:"Cancer is a leading cause of death in human beings. Surgery, chemotherapy, radiotherapy, immunotherapy, and biologically targeted therapy are common modalities for cancer treatment. However, cancer resistance is common in chemotherapy and often leads to therapeutic failure. This chapter addresses the role of apoptosis in tumor’s resistance to chemotherapy and the underlying mechanisms. Cancer cells are always resistant to apoptotic signals via a series of biochemical changes. Cancer cells are resistant to chemotherapeutic agents that are potent apoptosis inducers via multiple mechanisms, such as upregulated anti-apoptotic signals and downregulated pro-apoptotic signals, faulty apoptotic signaling, faulty apoptosis initiation and implementation, etc. We also discuss the possible approaches to overcoming cancer resistance to chemotherapy due to altered apoptosis.",book:{id:"6618",slug:"current-understanding-of-apoptosis-programmed-cell-death",title:"Current Understanding of Apoptosis",fullTitle:"Current Understanding of Apoptosis - Programmed Cell Death"},signatures:"Lichan Chen, Yanyun Zeng and Shu-Feng Zhou",authors:[{id:"229027",title:"Prof.",name:"Shu-Feng",middleName:null,surname:"Zhou",slug:"shu-feng-zhou",fullName:"Shu-Feng Zhou"}]},{id:"58369",title:"Reactive Oxygen Species in Skin Repair, Regeneration, Aging, and Inflammation",slug:"reactive-oxygen-species-in-skin-repair-regeneration-aging-and-inflammation",totalDownloads:2101,totalCrossrefCites:15,totalDimensionsCites:29,abstract:"As the most important and largest surface barrier, the skin provides a necessary protection to the organism from the external factors, including chemical, biological, and physical irritation, injury, and others. External environmental irritants or their metabolites are inherent oxidants and/or directly or indirectly drive the production of various reactive oxidants, reactive oxygen species (ROSs), owing to the redox imbalances. ROSs, the most common free oxygen radicals, participate in a series of physiological and pathological skin processes. Here, we discussed the role of oxidative events in injury, repair, photoaging, and cutaneous disease development. Intrinsic and extrinsic factors lead to the skin barrier damage, which leads to the disequilibrium in oxidant and antioxidant balance and induces excessive ROS production. The underlying mechanisms include DNA damage, MAPK/AP-1, NF-κB, and JAK/STAT-signaling pathways, apoptosis and autophagy, and autoimmune reaction of melanocytes and keratinocytes. The skin employs a number of antioxidant agents to protect the oxidative balance, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), ascorbic acid, and tocopherols. The results presented here indicate that antioxidant treatments may be effective when applied in the therapy of cutaneous diseases where oxidative stress plays a prominent pathogenic role.",book:{id:"6333",slug:"reactive-oxygen-species-ros-in-living-cells",title:"Reactive Oxygen Species (ROS) in Living Cells",fullTitle:"Reactive Oxygen Species (ROS) in Living Cells"},signatures:"Hui Xu, Yun-Wen Zheng, Qi Liu, Li-Ping Liu, Feng-Lin Luo, Hu-Chen\nZhou, Hiroko Isoda, Nobuhiro Ohkohchi and Yu-Mei Li",authors:[{id:"63284",title:"Prof.",name:"Nobuhiro",middleName:null,surname:"Ohkohchi",slug:"nobuhiro-ohkohchi",fullName:"Nobuhiro Ohkohchi"},{id:"216569",title:"Associate Prof.",name:"Yun-Wen",middleName:null,surname:"Zheng",slug:"yun-wen-zheng",fullName:"Yun-Wen Zheng"},{id:"216572",title:"Dr.",name:"Hui",middleName:null,surname:"Xu",slug:"hui-xu",fullName:"Hui Xu"},{id:"216574",title:"Dr.",name:"Qi",middleName:null,surname:"Liu",slug:"qi-liu",fullName:"Qi Liu"},{id:"216576",title:"Dr.",name:"Yu-Mei",middleName:null,surname:"Li",slug:"yu-mei-li",fullName:"Yu-Mei Li"},{id:"234877",title:"BSc.",name:"Feng-Lin",middleName:null,surname:"Luo",slug:"feng-lin-luo",fullName:"Feng-Lin Luo"},{id:"234878",title:"BSc.",name:"Zhou",middleName:null,surname:"Hu-Chen",slug:"zhou-hu-chen",fullName:"Zhou Hu-Chen"},{id:"234880",title:"Prof.",name:"Hiroko",middleName:null,surname:"Isoda",slug:"hiroko-isoda",fullName:"Hiroko Isoda"},{id:"234884",title:"Dr.",name:"Li-Ping",middleName:null,surname:"Liu",slug:"li-ping-liu",fullName:"Li-Ping Liu"}]},{id:"61053",title:"Adult Stem Cell Membrane Markers: Their Importance and Critical Role in Their Proliferation and Differentiation Potentials",slug:"adult-stem-cell-membrane-markers-their-importance-and-critical-role-in-their-proliferation-and-diffe",totalDownloads:1337,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The stem cells are part of the cells that belong to the stromal tissue. These cells remain in a quiescent state until they are activated by different factors, usually those generated by an alteration in the parenchymal tissue. These cells have characteristic membrane markers such as CD73, CD90, and CD105. Those are a receptor, which in response to their ligand induces strong changes in different metabolic pathways that lead to these cells, both to generate molecules with different activities and to leave their stationary phase to reproduce and even differentiate. This review describes the metabolic pathways dependent on these membrane markers and how they influence on parenchymal tissue and other stromal cells.",book:{id:"6658",slug:"stromal-cells-structure-function-and-therapeutic-implications",title:"Stromal Cells",fullTitle:"Stromal Cells - Structure, Function, and Therapeutic Implications"},signatures:"Maria Teresa Gonzalez Garza",authors:[{id:"181389",title:"Ph.D.",name:"Maria Teresa",middleName:null,surname:"Gonzalez Garza",slug:"maria-teresa-gonzalez-garza",fullName:"Maria Teresa Gonzalez Garza"}]}],onlineFirstChaptersFilter:{topicId:"171",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81298",title:"Roles of Extracellular Vesicles in Cancer Metastasis",slug:"roles-of-extracellular-vesicles-in-cancer-metastasis",totalDownloads:35,totalDimensionsCites:0,doi:"10.5772/intechopen.103798",abstract:"Extracellular vesicles (EVs) are biological active vesicles and carriers of information in intercellular communication. In cancer settings, EVs especially exosomes (Exo), play a focal role in modulating the tumor microenvironment mainly by increasing tumor proliferation, facilitating the crosstalk between tumor and tumor-neighboring cells, and influencing the host immune response. Amongst these functions in tumor growth, Exo modulate fundamental steps of tumor progression, such as growth, invasion, and immune modulation. On the endocrine level, Exo released from tumors were shown to mediate distant cell-cell communication processes via secretory factors and miRNAs, which result in the set-up of pro-tumorigenic microenvironments supportive of metastatic dissemination. This is achieved through processes such as fibroblast activation, extracellular matrix ECM production, angiogenesis, and immune modulation.",book:{id:"10796",title:"Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg"},signatures:"Eman Helmy Thabet"},{id:"80871",title:"Tumor-Derived Exosome and Immune Modulation",slug:"tumor-derived-exosome-and-immune-modulation",totalDownloads:54,totalDimensionsCites:0,doi:"10.5772/intechopen.103718",abstract:"Tumor cells, like most other cells, release exosomes called tumor-derived exosomes (TEX) and are vital for intercellular communication. TEX are membrane-bound extracellular vesicles (EVs), containing unique cargo reminiscent of the parent tumor cells and possess immunomodulatory functions. TEX carries factors that directly promote immunosuppression in the tumor microenvironment and indirectly attract immunosuppressive T-regulatory (Treg) cells. The tumor-secreted exosomes can transfer their cargo by multiple mechanisms like fusion, phagocytosis, and receptor-mediated endocytosis, activating the recipient cells. TEX directly engages and releases cytokines, inactivating natural killer (NK) cells and T-cells and activating apoptosis. Tumor-derived exosomes also release soluble factors to suppress dendritic cell (DC) maturation while activating the expansion of immune-suppressive cells like Myeloid-derived suppressor cells (MDSCs) and Regulatory T (Treg) cells. Several studies have shown the relevance of TEX containing tumor-associated antigens (TAA) in reducing the efficacy of cancer immunotherapy and adoptive cell therapy. Hence understanding the basic biology and mechanism of TEX-mediated immunosuppression is critical in discovering cancer biomarkers and finding better immunotherapy and cell therapy approaches. In this chapter, we have discussed TEX biogenesis, TEX’s structural and molecular features, TEX-mediated immunosuppression, and its relation to immunotherapy.",book:{id:"10796",title:"Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg"},signatures:"Deepak S. Chauhan, Priyanka Mudaliar, Soumya Basu, Jyotirmoi Aich and Manash K. Paul"},{id:"79834",title:"Morphology and Formation Mechanisms of Cellular Vesicles Harvested from Blood",slug:"morphology-and-formation-mechanisms-of-cellular-vesicles-harvested-from-blood",totalDownloads:60,totalDimensionsCites:0,doi:"10.5772/intechopen.101639",abstract:"Theoretical and experimental evidence on cellular vesicles (CVs) isolated from blood is presented. It is suggested that comparison of the observed shapes with theoretical shapes obtained by minimization of membrane-free energy in combination with electron microscopy is key in the assessment of CV identity. We found that shapes of CVs isolated from blood by repetitive centrifugation (up to 20.000 g) and washing, and observed by scanning electron microscopy (SEM) agreed well with theoretically observed shapes. It is indicated that these CVs are colloids deriving from residual blood cells, mostly platelets. SEM images of washed erythrocytes undergoing budding and transmission electron microscopy (TEM) images of isolated erythrocyte microvesicles likewise showed smooth shapes that we described as characteristic for colloidal CVs. Besides these, the CV isolates may contain other small particles, such as exosomes and viruses, as observed in isolates from tomato homogenate, however, we could not identify such particles in isolates from healthy human blood. Theory of deviatoric elasticity underlaying minimization of the membrane free energy and simulated two-component vesicles with the orientational ordering of anisotropic constituents are presented to indicate the interdependence of curvature—sorting of membrane constituents and their orientational ordering in strongly anisotropically curved regions.",book:{id:"10796",title:"Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg"},signatures:"Veronika Kralj-Iglič, Gabriella Pocsfalvi and Aleš Iglič"},{id:"80195",title:"Diversity of Extracellular Vesicles (EV) in Plasma of Cancer Patients",slug:"diversity-of-extracellular-vesicles-ev-in-plasma-of-cancer-patients",totalDownloads:81,totalDimensionsCites:0,doi:"10.5772/intechopen.101760",abstract:"Extracellular vesicles (EVs) are produced by all cells and are found in all body fluids. They function as intercellular messengers that carry and deliver signals regulating cellular interactions in health and disease. EVs are emerging as potential biomarkers of diseases and responses to therapies, and much attention is being devoted to understanding their role in physiological as well as pathological events. EVs are heterogenous in their origin, size, molecular characteristics, genetic content and functions. Isolation of EV subsets from plasma and characterization of their distinct properties have been a limiting factor in ongoing efforts to understand their biological importance. Here, we discuss the immunoaffinity-based strategies that are available for isolating distinct subsets of EVs from plasma and provide a road-map to their successful immunocapture and molecular profiling, with special attention to tumor-derived EVs or TEX.",book:{id:"10796",title:"Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg"},signatures:"Theresa L. Whiteside and Soldano Ferrone"},{id:"79955",title:"The Role of Extracellular Vesicles in Immunomodulation and Pathogenesis of Leishmania and Other Protozoan Infections",slug:"the-role-of-extracellular-vesicles-in-immunomodulation-and-pathogenesis-of-leishmania-and-other-prot",totalDownloads:111,totalDimensionsCites:0,doi:"10.5772/intechopen.101682",abstract:"Extracellular vesicles (EVs) have lately emerged as crucial mediators in parasite infections. Recent research suggests that protozoan parasites, including Leishmania, employ EVs as transport vehicles to deliver biologically active effector molecules such as parasitic virulence factors to modulate the host immune system and their microenvironment. The immunomodulatory effects of EVs play an essential role in the formation and progression of parasitic diseases. The immunomodulatory strategies applied by EVs of protozoan origin have similarities to the development and progression of other infections or diseases such as cancer. In this chapter, we will provide recent insights into the role of EVs in host-pathogen interactions, intercellular-communication, immunomodulation and pathogenesis of Leishmania and other protozoan parasites, including Plasmodium spp., Toxoplasma spp. and Trypanosoma spp. In addition, biologically inspired by the immunomodulation strategies of protozoan parasites, new immunotherapeutic models are being currently investigated to implement EVs more intensively in both therapy and diagnostics. Therefore, besides highlighting the role of EVs in protozoan infections, this chapter sheds light briefly on new immunotherapeutic approaches utilizing the strategies of protozoan EVs in medicine.",book:{id:"10796",title:"Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg"},signatures:"Zeynep Islek, Batuhan Turhan Bozkurt, Mehmet Hikmet Ucisik and Fikrettin Sahin"},{id:"80126",title:"Extracellular Vesicles as Biomarkers and Therapeutic Targets in Cancers",slug:"extracellular-vesicles-as-biomarkers-and-therapeutic-targets-in-cancers",totalDownloads:103,totalDimensionsCites:0,doi:"10.5772/intechopen.101783",abstract:"Extracellular vesicles refer to exosomes, apoptotic bodies, microvesicles and large oncosomes, which are membrane bound structures secreted by cells including cancer cells. The pathological role and translational potential of extracellular vesicles (EVs) in cancers are receiving research attention recently. The cargoes of cancer-derived EVs retain the molecular properties of their sources and cancer cells actively release EVs into body fluids that are easy to access. EVs released from cancer cells not only promote cancer progression through the delivery of cancer-associated molecules but also reflect alterations in the state of cancers during therapy. They are considered promising biomarkers for therapeutic response evaluation, especially resistance to therapy and diagnostics. This chapter discusses the various roles of extracellular vesicles in cancers and their potential as therapeutic targets.",book:{id:"10796",title:"Extracellular Vesicles - Role in Diseases, Pathogenesis and Therapy",coverURL:"https://cdn.intechopen.com/books/images_new/10796.jpg"},signatures:"Prince Amoah Barnie, Justice Afrifa, Eric Ofori Gyamerah and Benjamin Amoani"}],onlineFirstChaptersTotal:16},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:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:315,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,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. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"June 25th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",slug:"robert-koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"7",title:"Bioinformatics and Medical Informatics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",isOpenForSubmission:!0,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},{id:"8",title:"Bioinspired Technology and Biomechanics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",isOpenForSubmission:!0,editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",slug:"adriano-andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",biography:"Dr. Adriano de Oliveira Andrade graduated in Electrical Engineering at the Federal University of Goiás (Brazil) in 1997. He received his MSc and PhD in Biomedical Engineering respectively from the Federal University of Uberlândia (UFU, Brazil) in 2000 and from the University of Reading (UK) in 2005. He completed a one-year Post-Doctoral Fellowship awarded by the DFAIT (Foreign Affairs and International Trade Canada) at the Institute of Biomedical Engineering of the University of New Brunswick (Canada) in 2010. Currently, he is Professor in the Faculty of Electrical Engineering (UFU). He has authored and co-authored more than 200 peer-reviewed publications in Biomedical Engineering. He has been a researcher of The National Council for Scientific and Technological Development (CNPq-Brazil) since 2009. He has served as an ad-hoc consultant for CNPq, CAPES (Coordination for the Improvement of Higher Education Personnel), FINEP (Brazilian Innovation Agency), and other funding bodies on several occasions. He was the Secretary of the Brazilian Society of Biomedical Engineering (SBEB) from 2015 to 2016, President of SBEB (2017-2018) and Vice-President of SBEB (2019-2020). 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His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. 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