Different theranostic agents used for biomedical applications.
\r\n\tAnimal food additives are products used in animal nutrition for purposes of improving the quality of feed or to improve the animal’s performance and health. Other additives can be used to enhance digestibility or even flavour of feed materials. In addition, feed additives are known which improve the quality of compound feed production; consequently e.g. they improve the quality of the granulated mixed diet.
\r\n\r\n\tGenerally feed additives could be divided into five groups:
\r\n\t1.Technological additives which influence the technological aspects of the diet to improve its handling or hygiene characteristics.
\r\n\t2. Sensory additives which improve the palatability of a diet by stimulating appetite, usually through the effect these products have on the flavour or colour.
\r\n\t3. Nutritional additives, such additives are specific nutrient(s) required by the animal for optimal production.
\r\n\t4.Zootechnical additives which improve the nutrient status of the animal, not by providing specific nutrients, but by enabling more efficient use of the nutrients present in the diet, in other words, it increases the efficiency of production.
\r\n\t5. In poultry nutrition: Coccidiostats and Histomonostats which widely used to control intestinal health of poultry through direct effects on the parasitic organism concerned.
\r\n\tThe aim of the book is to present the impact of the most important feed additives on the animal production, to demonstrate their mode of action, to show their effect on intermediate metabolism and heath status of livestock and to suggest how to use the different feed additives in animal nutrition to produce high quality and safety animal origin foodstuffs for human consumer.
",isbn:"978-1-83969-404-2",printIsbn:"978-1-83969-403-5",pdfIsbn:"978-1-83969-405-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"8ffe43a82ac48b309abc3632bbf3efd0",bookSignature:"Prof. László Babinszky",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10496.jpg",keywords:"Technological Feed Additives, Feed Industry, Quality of Compound Feed, Non-Antibiotic Growth Promoter, Product Quality, Additive Enzymes, Digestibility of Nutrients, NSP Enzymes, Farm Animals, Livestock, Immunity, Microbiome",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 24th 2020",dateEndSecondStepPublish:"December 22nd 2020",dateEndThirdStepPublish:"February 20th 2021",dateEndFourthStepPublish:"May 11th 2021",dateEndFifthStepPublish:"July 10th 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Professor Emeritus from the University of Debrecen, Hungary who authored 297 publications (papers, book chapters) and edited 3 books. Member of various committees and chairman of the World Conference of Innovative Animal Nutrition and Feeding (WIANF).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.jpg",biography:"László Babinszky is Professor Emeritus of animal nutrition at the University of Debrecen, Hungary. From 1984 to 1985 he worked at the Agricultural University in Wageningen and in the Institute for Livestock Feeding and Nutrition in Lelystad (the Netherlands). He also worked at the Agricultural University of Vienna in the Institute for Animal Breeding and Nutrition (Austria) and in the Oscar Kellner Research Institute in Rostock (Germany). From 1988 to 1992, he worked in the Department of Animal Nutrition (Agricultural University in Wageningen). In 1992 he obtained a PhD degree in animal nutrition from the University of Wageningen.He has authored 297 publications (papers, book chapters). He edited 3 books and 14 international conference proceedings. His total number of citation is 407. \r\nHe is member of various committees e.g.: American Society of Animal Science (ASAS, USA); the editorial board of the Acta Agriculturae Scandinavica, Section A- Animal Science (Norway); KRMIVA, Journal of Animal Nutrition (Croatia), Austin Food Sciences (NJ, USA), E-Cronicon Nutrition (UK), SciTz Nutrition and Food Science (DE, USA), Journal of Medical Chemistry and Toxicology (NJ, USA), Current Research in Food Technology and Nutritional Sciences (USA). From 2015 he has been appointed chairman of World Conference of Innovative Animal Nutrition and Feeding (WIANF).\r\nHis main research areas are related to pig and poultry nutrition: elimination of harmful effects of heat stress by nutrition tools, energy- amino acid metabolism in livestock, relationship between animal nutrition and quality of animal food products (meat).",institutionString:"University of Debrecen",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Debrecen",institutionURL:null,country:{name:"Hungary"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"25",title:"Veterinary Medicine and Science",slug:"veterinary-medicine-and-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"185543",firstName:"Maja",lastName:"Bozicevic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/185543/images/4748_n.jpeg",email:"maja.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"7144",title:"Veterinary Anatomy and Physiology",subtitle:null,isOpenForSubmission:!1,hash:"75cdacb570e0e6d15a5f6e69640d87c9",slug:"veterinary-anatomy-and-physiology",bookSignature:"Catrin Sian Rutland and Valentina Kubale",coverURL:"https://cdn.intechopen.com/books/images_new/7144.jpg",editedByType:"Edited by",editors:[{id:"202192",title:"Dr.",name:"Catrin",surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland"}],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:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"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"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],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. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"62778",title:"Static Var Compensator with Fractional Order Dynamics for Enhanced Stability and Control",doi:"10.5772/intechopen.79615",slug:"static-var-compensator-with-fractional-order-dynamics-for-enhanced-stability-and-control",body:'\nIn recent times, the demand and the importance of a robust transmission network is increasing at an extraordinary rate. With the advancement of the society, it is vital to ensure the enough power availability to both the common consumer and the industry. The conventional transmission system has several disadvantages that include the lack of its operation on full load capacity, performance degradation under heavy inductive loads, and voltage sagging problems. Moreover, the conventional transmission system is not efficient in resolving and isolating the fault over the lines because most of the power systems are controlled through mechanical means. A more preferable alternative to the fixed mechanical control of the transmission network is the flexible AC transmission system (FACTS). All FACTS controllers are operated in a closed loop fashion and a detailed comparison of several control schemes is presented in the work given in [1].
\nThe shunt compensators are preliminarily used for the reactive power compensation over the transmission network system. The reactive power is supplied or absorbed using the electronic drive-based shunt flexible ac transmission system (FACTS) controllers including the static Var compensator (SVC) and STATCOM [2, 3]. Over a transmission network bus voltage stability is a prime issue and it needs to be addressed for the overall stability of the power network. The bus voltage over a transmission network is subject to the variations due to the stochastic nature of variable inductive load demands. The bus voltages are much dependent on the reactive power demands [3]. The utilization of the SVC as shunt compensation for voltage management and related concepts are discussed by the authors of reference [4]. SVC has a simple structure, which provides controlled reactive power compensation over the transmission network. Other shunt compensator such as static synchronous compensator (STATCOM), which is based on the power electronics converter concept, is an advanced version of the FACTS controllers [5]. The power electronics-based shunt compensator can provide dynamic stability of the power network over a wider range as compared to the conventional SVC-based system. However, the closed loop control structure in case of the power electronics-based FACTS controller is more complex as compared to the SVC. In [6], the authors proposed a coordinated control strategy for the dynamic stability of the SVC-based power network. In order to enhance the transient stability, damping of power oscillations, and economic operation of the power network, several researchers have proposed the utilization of the unified power flow controller (UPFC) that simultaneously provide the series and shunt compensation over the transmission network [7, 8]; however, the structure of the closed loop control system is very complex for the UPFC. Moreover, the solution is very costly as compared to the conventional SVC-based power system. Different applications of the UPFC and STACOM controllers in the power networks have been discussed in detail by the authors of Ref. [9, 10, 11]. Apart from the applications of the FACTS controllers, another important issue is to choose the optimal location for the installment of these controllers [12]. A detailed review on the optimal placement of the FACTS devices is presented in [13]. Apart from the benefits of the FACTS controllers, feedback system plays vital role in achieving the control objectives. Several integer order robust control methods have been proposed for the SVC-based power system control problem. The detailed discussion of the power flow stability using closed loop FACTS controllers are discussed by the authors of [14, 15, 16, 17]. In the above cited work, the authors proposed several control techniques such as adaptive backstepping, fuzzy logic; Lyapunov-based nonlinear controller and the H∞ Control. In [18], the authors have proposed robust variable structure control system for the SVC-based power system. An important issue in the design of any control system is how to select the optimal parameters. Different approaches are used in the literature such as PSO-based parameters optimization [19] and genetic algorithm-based parameters selection in [20, 21, 22, 23, 24]. In [25, 26], two different variants of the robust controllers have been proposed for VSC-based HVDC system. Fractional calculus is finding numerous applications in the area of the modeling and control of the dynamic systems. Fractional order systems have some additional advantages over integer order systems such as high degree of freedom in the parameters selection, robustness to noise, offer less chattering in the control signal, and wide stability margins [27]. In [28, 29], the authors proved that the fractional order systems are stable even when the systems roots lie in the right half of the complex plane. The formulation of fractional order controllers based on fractional order models offer additional advantages such as reduced computational costs and more robustness against uncertainties [30, 31]. Several authors proposed fractional order model-based controllers such as robotic manipulators [32], thermal modeling of buildings [33], aircraft [34], and pneumatic actuators [35]. Based on the above literature survey, it is concluded that the wider stability region concepts of the fractional order systems can be applied in several fields of interests. Particularly, the fractional order dynamics can be introduced to the SVC-based power system dynamic systems for enhanced stability margins. Fractional order filters consisting of inductive and capacitive elements have been practically realized and discussed in the literature. Fractional order tunable resonators and filters have been practically realized and the details are given in [36]. Electronically tunable all pass filter has been proposed and discussed in [37].
\nThis chapter proposes static Var compensator (SVC) using fractional order inductive and capacitive elements. The idea is exploited theoretically and the dynamic equation of the fractional order susceptance is derived. Finally, a novel fractional order sliding surface is proposed and a feedback controller is derived for the bus voltage stabilization problem of power transmission network. The parameters of the proposed control scheme are tuned using Simulink response optimization tool box.
\n\nFigure 1 shows the block diagram of the fractional order SVC-based power system. Before going into the details of the mathematical models of fractional order SVC, this section presents the definitions of the fractional calculus.
\n(a) Configuration of fractional SVC (TCR-FC), (b) single machine infinite bus configuration.
Basic definition of the fractional operator can be denoted by a general fundamental operator \n
Here \n
Riemann–Liouville formula of the αth-order fractional integration can be written by
\nHere \n
The GL definition is given as:
\nHere, h represents the time step that is increasing with time and [.] is the integer part,
\n\nTheorem 1: The following equation shows an autonomous system [29]:
\n\nHere α is differential order, \n
From Figure 2, it is clear that the fractional order systems with the fractional orders range of 0–1 have wider stability margins as compared to the integer order systems.
\nStability region of (a) integer order system (b) fractional order system with order between 1 and 2 (c) fractional order systems with order between 0 and 1.
The goal of this work is to include the fractional components in the SVC mathematical model [18]. In order to modify the conventional design of TCR-FC type SVC, the fractional order inductor and capacitor are used to analyze and improve the system performance. Controllable part of the SVC is the susceptance, so the mathematical model derived in this section shall be represented in terms of the susceptance (B). The block diagram of the system and single machine infinite bus configuration is shown in Figure 1a and b.
\nFor the integer type of SVC-based power system, the expression of the susceptance is expressed as [18].
\nIn Eq. (8), \n
In Eq. (9), \n
Here \n
The voltage dynamics across a fractional inductor is written as
\nCombining Eqs. (12) and (11) yields the fractional order susceptance of the inductor as
\nBy multiplying the operator \n
Using Eq. (14), and by equating \n
The voltage and the current dynamics across the fractional capacitor is written as \n
The fractional capacitive susceptance is written as
\nSimplifying Eq. (17) yields
\nBy combining Eqs. (10), (15) and (18), one obtains
\nThe modified state space representation of the power system with the fractional order SVC-based system configurations written as
\nIn Eq. (20), \n
The control objective is to formulate a robust control system for the fractional order SVC-based power system that must behave as insensitive to the disturbances and uncertainties, thus ensure a stabilized voltage over the transmission lines. Thus, the control objective is the regulation of the bus voltage \n
In the above expressions \n
By combining Eqs. (20) and (22), one obtains
\nThe control law is derived as
\nThe following inequality holds [30].
\nHere \n
Using Eq. (25), we can simplify Eq. (26) as
\nUsing Eqs. (23) and (27), \n
By combining Eqs. (24) and (28), one obtains
\nThe first term of Eq. (29) is negative, so if the discontinuous gain \n
\nLemma 1. If integral of the fractional derivative \n
Here \n
\nLemma 2. The fractional integral operator \n
From Eq. (29) it is proved that the sliding surface is zero, that is, \n
Multiplying Eq. (32) by \n
Using Lemma 1, Eq. (33) can be expressed as
\nAt time \n
Eq. (35) can be expressed as
\nUsing Lemma 1, Eq. (36) is expanded as
\nApplication of Lemma 2 to the right hand side of Eq. (37) yields
\nCombination of Eqs. (37) and (38) yields
\nIf \n
From Eq. (40), one obtains
\nFrom Eq. (41), it is proved that the error will converge near to the equilibrium points in finite time.
\nMATLAB/Simulink offers built-in response optimization tool box, which is extensively used for the optimal parameters selection of the control system [38]. To start the GUI, go to analysis tab of the simulink and click response optimization tool box. Define the parameters to be optimized in the MATLAB workspace. Then, use the response optimization tool box for importing the workspace defined parameters as design variables. The minimum and maximum search space of the design variables are adjusted. In the second step, the input reference signal is defined and imported using the toolbox. Finally, the output signal is imported from the simulink model that will follow the reference imported signal such that the error between the two signals is minimum. The error is minimized in an iterative manner and in this case, the error signal is the cost function. While minimizing the cost function, the parameters of the control system are adjusted online. The toolbox is associated with different optimization methods such as pattern search, simplex search, and gradient descent methods [39, 40].
\nThe derived fractional order control system is shown in Eq. (24). For best control performance, it is vital to choose the optimal control parameters. This work compares the performance of the proposed controller (Eq. 24) to the conventional PID control system. The parameters of the proposed control scheme are optimized using Latin Hypercube method and Simulink response optimization toolbox. The order of the fractional operator is chosen constant as \n
To optimize the parameters, the cost function chosen is the integral of square of the error (ISE) between the reference command and the feedback signal. The initial values of the controller parameters are chosen as \n
Optimized parameters of the proposed scheme.
Step response optimization.
The step response and optimized parameters of the PID controllers are shown in Figures 5 and 6. Figure 5 shows the response of the system with optimized PID under nominal conditions. The optimal parameters are given in the table of Figure 6.
\nPID step response optimization.
Parameters of the optimized PID controller.
For numerical simulations, the nominal parameters of the power system including the SVC configuration are given as following [18]: \n
MATLAB/SIMULINK simulation setup.
Load demand profile.
The control performance of the SVC-based power system under the step response is compared in Figure 9. The comparison is done for the error of the bus voltage stabilization response under the proposed fractional order control system and optimized PID. From the simulation results, it is concluded that the proposed control system is more robust against the load demand variation profile as compared to the optimized PID control system.
\nStep response error (a) proposed scheme (b) optimized PID.
In this section, the bus voltage tracking performance of the SVC-based power network is compared under the action of the proposed control and the optimized PID. The comparative results are shown in Figure 10. From the results provided, it is clear that the system under the proposed control scheme perfectly tracks the reference command while the system under the PID controller exhibits tracking errors of considerable magnitudes.
\nTracking response (a) proposed scheme (b) optimized PID.
The system’s bus voltage stabilization under heavy inductive loads is compared under the action of the proposed control and the optimized PID. The simulation results are shown in Figure 10. The inductive load is varied gradually from time t = 60 sec and increased step wise till t = 100 sec. The proposed controller is robust against the dynamics introduced due to the heavy inductive loads. From Figure 11, it is clear that the response of the power system with PID-based SVC system suffers from voltage sage condition. The proposed controller-based SVC system is efficient in handling the situation and thus, the bus voltage error is very small with no voltage dips.
\nStep response under heavy inductive loads (a) proposed scheme (b) optimized PID.
The control signals comparison is given in Figure 12. The proposed control system offers low frequency oscillations, which shows the robustness of the proposed method as compared to the PID method. Usually, in classical sliding mode control method, the robust term excites high frequency oscillations. Due to the high frequency oscillations, the classical sliding mode control is not feasible for practical implementations. The proposed control method is noninteger in nature and from the control law given in Eq. (24), there is an integral term around the robust term, that is, signum function. So, it excites low frequency oscillations and thus it is very feasible for practical implementation over the microprocessor.
\nControl signal comparison.
In this chapter, a fractional order SVC-based power system is discussed. Based on the fractional sliding manifold, a fractional order sliding control system is proposed. The robustness of the proposed control system is tested under the variable load demand and heavy inductive loading. The performance of the proposed control system is compared with a classical PID control system. From the results and discussion section, it is clear that the proposed control system is more robust as compared to the classical PID control under nonlinear loading profile. Moreover, the control chattering phenomenon is significantly reduced. The proposed control system is feasible for practical implementations.
\nThe authors are thankful to the University of Technology Nowshera, Pakistan for providing the financial support for the publication of this chapter.
\nCancer has a major impact on society across the world. Estimated number of new cases of cancer, current cases of cancer, deaths, survival rate, mortality and in depth information, symptoms of cancer, its early detection, prevention and treatment all are provided by American Cancer Society. Nearly 13% of cancer diagnosed in 2017 was in the young at age of 20. The new review statistics shows 28 types of rare cancer which talks about mortality rate, survival, diagnosis and also provides an idea about symptoms and risk factors related to different types of cancer [1].
Therapeutic approaches such as development of nanoemulsions, liposomes, microspheres and nanoparticles have facilitated in fighting cancer. Among these, the simplest platforms are the nanoemulsion having size range of 100 to 500 nm which are kinetically stabilized having high content of oil and low amount of surfactant [2]. Solubility of poorly soluble drugs [3, 4] and its bioavailability can be increased by converting the drug into forms like capsule and gels [5] or can be used in their original form. The method used for the fabrication of nanoemulsion are high energy methods (microfluidization and sonication) and low energy emulsification method [6, 7, 8].
Theranostics is a term originally coined to define an approach that combine’s diagnostics with therapeutics [9]. It embraces multiple techniques to arrive at comprehensive diagnosis, molecular images and an individualized treatment regimen [10, 11]. Recently, there is an effort to tangle the emerging approach with nanotechnologies, in an attempt to develop theranostic nanoplatforms and methodologies [12]. Given that cancer is a highly heterogeneous and adaptable disease, diverse types of treatment options need to be chosen depending on patient’s characteristics and disease progression.
Drugs or methods that are used for accompanying diagnosis and cure [13] are referred to as Theranostics. One of the achievements of nanotechnology is the fabrication of theranostic nanomedicine for the preparation of these types of drugs. The term defines “a nanotherapeutic system which can deliver targeted therapy and diagnose”. This aspect provides help when fabricating nano based image contrasting agent and also in image guided therapeutics [14].
Rapid drug development, advanced disease management, reduced associated risk and cost are assumed to be the result of mutual techniques. Such type of investigation which involves quick diagnosis and treatment are very helpful in disease which are a major cause of morbidity and/or mortality and cancer is one of the disease and coincidently the initial research in theranostic is dedicated to oncology. Sound knowledge, core understanding of detection and therapy mechanism are required for the formation of theranostic agents. In order to fabricate theranostic agents one should have understanding of diagnostic strategies, molecular mechanism adverse effect and toxicity of material and techniques for nanoparticles preparation for therapy and diagnostic purpose.
Research in theranostics has rapidly improved in the past decade resulting into preparation of different contrast media and active ingredient with different method of preparation. Preparation of dual purpose nanoparticle system is the main aim of theranostics. Therefore it is important to put attention on all factors that influences the process, right from the preparation of nanoemulsion/nanoparticle till the removal of metabolites of the active molecules and other materials used. The factors can be the compatibility between chemicals, the condition in which the formulation is prepared, modification in formulations because of selected route of administration, the toxicity, metabolites of active ingredient, its biocompatibility and biodegradability and evaluation of pharmacodynamic and pharmacokinetic parameter and eventually the disadvantage and benefits of the process.
The basis of diagnosis in theranostics depends upon using different contrast agent during imaging. MRI is the most studied and used technique among all different imaging mechanism and a lot has been spent on research related to magnetic particles used as contrasting agent. Metals like gold, silver, iron oxide have been studied with the object of finding suitable particle for imaging with least toxicological effect. Diseased tissue and healthy tissue are differentiated in MRI by the use of these particles.
As stated one of the brutal disease is cancer and hence theranostic research has put an eye on this area. Day by day the research is going on in positive direction and much useful research has already been carried out. In order to understand the concept of diagnosis of cancer and therapy related to it the use of nanoparticle agents is in progression [27, 28]. One such example of theranostic agent is manganese oxide nanoparticle carrying drugs and contrast agents [29] and silica nanoparticle with magnetic and fluorescent tags [30]. In the past few years, combination of metal nanoparticle or shells [31, 32, 33] with magnetic components has yielded different theranostic agents for biomedical applications which are widely used. Some examples of theranostic agents are given in Table 1.
Contrast agent | Drug used | Applications | Size | Zeta potential | References |
---|---|---|---|---|---|
Manganese oxide | siRNA | MRI plus RNA delivery | — | — | [15] |
Gold | DOX Diagnosis | tumor targeting and PTT | 45.97 nm and 6.3 nm | −3.54 mV | [16, 17, 18] |
Iron oxide | siRNA, DOX, docetaxel | Targeting, MRI and therapy | 30 nm | −5 mV | [19, 20, 21] |
Silica | Pyropheophorbide (HPPH), DOX | Drug carrier, X-ray/CT imaging, Photodynamic therapy | 30 nm and 126 nm | −39 mV | [22, 23] |
CNTs | DNA plasmid, DOX, PTX | Diagnosis, DNA and drug delivery | 20 nm and 120.6 nm | — | [24, 25] |
QDs | DOX, MTX | Imaging, therapy and sensing | — | — | [26] |
Different theranostic agents used for biomedical applications.
Abbreviations: siRNA: short interfering ribonucleic acid, CNTs: carbon nanotubes, QDs: quantum dots, DOX: Doxorubicin, HPPH: 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-alpha, MTX: Methotrexate, PTX: Paclitaxel, MRI: Magnetic resonance imaging, CT: Computed topography.
Theranostic nanosystems comprise of platforms/nanocarriers that are used as imaging as well as therapeutic agents via a single entity. Nanotheranostic devices can be made by many types of inorganic and organic nanomaterials. Preclinical implementations make use of nanotheranostic system because they might provide a way or method of understanding many crucial aspects of drug delivery and how these systems can assist in knowing the power of personalized medicines.
At present radiotherapy, surgery and chemotherapy are possible treatments for cancer patients. The purpose of the theranostic is to use these therapeutic strategies and reduce the risk associated with chemotherapy and radiotherapy and in addition to it avoid complications related to surgery and trauma. In addition, with the help of nanotechnology, theranostics may support the diversification of therapeutic approaches like PTT, PDT and immunotherapy. Here we report some of these therapeutic strategies often used in theranostics, like radiotherapy, chemotherapy, PDT, PTT and immunotherapy.
Anticancer drugs have proven beneficial in improving survival rate of cancer patients [34]. There are huge numbers of clinical anti-cancer drugs which are broadly applied to theranostics. On the basis of structure and resource of chemotherapy drugs, cancer therapeutic agents can be classified into six types: alkylating agent, antitumor antibiotic, phytogenic anticarcinogen, antimetabolites, hormone and miscellaneous anti-cancer drugs. Thermo DOX for liver cancer, Doxil for ovarian cancer therapy and Myocet for metastatic breast cancer are few cancer nanomedicines that have been approved by the FDA. Theranostic systems also make use of prodrugs like platinum (IV) prodrug to reduce the toxicity of drug and by increasing the active hits to the cells of tumors site. Due to their broad availability these prodrugs are very popular option. The UV light is transformed from NIR light by UCNP which activates the prodrugs to highly toxic platinum (II) complexes that enters the cell by endocytosis after grafted onto up converting nanoparticles (UCNP) [35]. In order to attain best therapeutic efficacy of drug delivery systems a high payload is essential. In theranostics, in order to maintain the original size and solubility in aqueous media a carrier with large pore volume and surface area are given preferences so that more therapeutic agent can be carried [36]. For example, Sorafenib with a loading ration of 28.2% can be loaded on porous silica nanoparticles and may release the therapeutic agent in sustained fashion [37]. GO, Ws2 and MoS2 are some of the popular 2-D nanomaterials that have a very high drug payload as they can bear chemotherapeutics on both sides of sheet. Some of the example of high drug payload include 118% for 7-ethyl-10-hydroxycamptothecin (SN38) and approx 239% for DOX were observed on MoS2 [38], DOX (approximately 400%) on GO [39] was also significant. Cancer cells show multidrug resistance (MDR) often when they are treated by single drug which can be overcome by employing efficient strategies of theranostics. By combining P-glycoprotein (P-gp) reversing agent with anticancer drug the hurdle of MDR can be resolved [40]. The function of P-gp reversing agent is to avoid the pumping of chemotherapeutic drugs out of cancer cells due to over expression of P-gp. One way to overcome MDR is by covering the positive change that is present on anticancer drugs. DOX alone cannot produce significant cancer effect but when it is adsorbed on the surface of polymeric nanoparticle more chance are there that cancer cell may readily uptake it and accumulate within cancer cell and produce more cytotoxicity to cancer cell. Nanocarriers loaded with combination of anticancer drugs provide synergistic effect thereby improving overall management of cancer [41, 42].
Microwave, light irradiation or magnetic field can potentiate the effect of thermal therapy which in turn employs hyperthermia to kill cancer cells. Among all the above mentioned therapies photothermal therapy has the maximum capacity to destroy cancer cell while causing least damage to nearby healthy cells. Localized hyperthermia under light irradiation at tumor site is generated by using NIR absorbing agent in photothermal therapy [43]. In MR region an ideal PTT agent should show strong absorbance and must exhibit less fluorescence quantum yield thereby promoting efficient conversion of absorbed light energy into heat via non-radiative transition rather than fluorescence emission.
Inorganic nanoparticles and organic dyes are extensively employed as PTT agents. Examples of organic dyes include Prussian blue, IR780, ICG, IR820, Cypate, IR825. These organic dyes have an added advantage of ease of loading on nanoplatforms and ideal NIR absorbance [44]. In order to improve the photostability and targeting ability of organic dyes they are being encapsulated into nanocarriers [45]. Carbocyanine dyes namely cypate and ICG were loaded into the polymeric micelle with loading rate of 50% and 20% for cypate and ICG respectively. Upon comparing loaded theranostic polymeric micelle with carbocyanine dye alone showed marked cellular uptake and longer retention time at the site of tumor. Remarkable PTT results were observed along with increased photothermal effect and photostability of organic dyes when nanomaterials like graphene derivatives absorbing strongly in the NIR regions were employed [46]. In NIR and PTT imaging techniques both cypate and ICG can be used as theranostic agents.
Photothermal conversion efficiency will decrease in presence of high fluorescence quantum yield and fluorescence imaging is disturbed in case of low quantum yield hence there is not much surety in theranostic application of organic dyes. Apart from the organic dyes, a wide range of inorganic nanoparticles have been fabricated for theranostic applications. Inorganic nanoparticles exhibit strong photothermal conversion efficiency and NIR absorption for PTT. It encompasses customized gold nanostructure like nanoshell, nanocages, nanorods and nanotubes. On comparing the gold nanorods alone against gold nanorods coated with Pt nanodots, the latter showed significant better photothermal effect than the former [47]. And the better results were due to the presence of Pt shell in the endosomes which not only prevented the original sharp LSPR band of gold nanorods from shifting and dampening but also prevented the aggregation of gold nanorods. Carbon nanotubes [48], carbon dots [49], GO are some of the other nanomaterials that can used for PTT. GO for in-vivo PTT was used for the first time by Liu group. Further they reduced the GO to rGO which had 7 times more NIR absorption than GO hence increasing the PTT effect [50]. PTT for now might only be used for treating skin cancer and not for internal cancer because of limiting light penetration depth but its noteworthy therapeutics capacities with minimum possible side effect cannot be ignored. Further study is required to get deeper insight about how phototoxicity is caused by PTT.
Apart from PTT, hyperthermia induced magnetically is also one of the non-invasive procedures to treat cancer [51]. Dielectric constant and microwave frequency between malignant tissue and normal tissue in breast can be employed for the detection and treatment of breast cancer. Dielectric contrast is used for scattering of an illuminating microwave signal and the incident microwave produces hyperthermia thereby treating malignant tissues [52].
Photosensitizers (PSs) used in PDT plays a vital role in the treatment of cancer and possess enormous potential. Cytotoxic reactive oxygen species or free radicals are generated when the molecular oxygen surrounding the diseased cell reacts with the absorbed light that is being transferred by PSs under laser irradiation which finally causes cell apoptosis and damage to cancerous cells [53]. No side effects are observed from photosensitizes and generate ROS only when laser light is irradiated upon them.
PDT requires low light density to cause damage to cancer cell unlike the PTT which requires high density laser light to generate hyperthermia that can cause damage to cancer cells [54]. PDT encompasses noteworthy advantages like very less invasiveness, on repeating the therapy is show no cumulative toxicity, very less damage to immune and hemopoietic system thereby improving the overall health and contributing to quality life for the patient. An ideal PS must have following properties like triplet state formation of high quantum yield and a good amount of triplet lifetime so that interaction with ground state oxygen is possible thereby generating sufficient ROS. However many PSs does not have good tumor selectivity, good amount of photosensitivity and absorption maxima above 700 nm [55]. A distinctive NIR absorption at 700 nm was observed by the help of extra axial mob linkers in monosubstituted phthalocyanine [56] that produced 20 nm red shift of characteristic Q band. PEG functionalized iron oxide nanocluster surface when loaded with Ce6 the absorption peak of chlorine e6 (Ce6) showed red shift from 650 nm to 704 nm [57]. The energy transferred from UCNPs to PSs are able to excite the combination of PSs and UCNP’s, therefore inhibiting the growth of tumor by generation of cytotoxic singlet oxygen [58].
Radiation therapy has become an integral part to treat many sarcomas. The mechanism of action of radiation therapy is that the radiation damages strings of DNA in the nucleus of cells which stops the cell multiplication. Apart from aforementioned functions of radiation therapy, it also produces reactive oxygen therapy (ROS) which indirectly damages the tumor cell and also damages the DNA of mitochondria and other organelle of cell. In case of surgical resection, the survival could be prolonged by employing radiation therapy. However due to frequent and repeated high dose of X-ray irradiation that causes systemic side effects and resistance to radiation had been noticed in cancerous cells.
Metal nanoparticles in strong association with strong capacities of photoelectric absorbance are used as radiation dose enhancing agents. For example research shows that radio sensitization is being mediated by Gold NP due to greater energy deposition and absorption in surrounding tissue from photoelectrons. Radiotherapy with prolonged circulation time in blood has been demonstrated by Auger electrons and characteristic X-rays [59] and polyethylene glycosylation modified gold nanoparticle (N GNPs). Radiotherapy can relieve the symptoms and prolong the lives of terminal cancer patients. However radiotherapy is not an easy task and may cause loss of organ functions also as it may also induce many complications. Moreover, it cannot completely remove cancer cells. In coming future we may see highly accurate and precise exposure of tumor site to high radiation by the application of radiation wave knife for much better clinical results.
After radiotherapy, surgery or chemotherapy it has been observed that a small number of cancer cells may still remain alive and in addition to it the overall treatment quality is also decreased due to drug resistance. Immunotherapy has great potential to treat cancer as it acts on the immune system rather than on the tumor itself. Immunotherapy is considered as a unique and promising strategy for cancer therapy [60] and the main advantages include its specific promotion on immune cells only aiming on target cells or target tissues. So far, the related investigations have been gradually transformed from laboratory research to clinical practice. For clinical treatment the use of immunotherapeutic drugs such as immune checkpoint inhibitors and T cells have been approved by FDA and have great potential for cancer treatment. Improved immunotherapeutic nanomaterials loaded with antigens, immune adjuvants and nucleic acids have been demonstrated to be helpful. The nanoplatforms may affect and alter immune cell actions and response non-specifically. They may easily damage the cancer cells and achieve tumor targeting with pathogens factors. For e.g. repetitive and homogenous antigens conjugated with gold nanoparticles are able to trigger immune response in an in-vitro setting even without the use of adjuvant. Recently a combination of IR phthalocyanine dye IR700 with monoclonal antibodies had been fabricated and this novel technique is known as Photoimmunotherapy [61]. Least side effect and significantly fast cell necrosis rate is observed when antibodies bind to target tumor cells during the PIT and is activated by NIR light irradiation. Hence for monitoring and treating cancer in a highly selective manner PIT is a good theranostic approach.
Conventional cancer therapies often do not succeed to eradicate tumor completely. In order to recover anticancer efficacy, the arrangement of two or more therapeutic modalities such as chemo photodynamic, photothermal photodynamic, chemo photo thermal synergistic formulations have been explored. Thermomotherapeutic characteristics in association with theranostic methods result in development of anticancer drug that possess synergistic therapeutic effect [62]. Chemotherapy could be improved by the use of photothermal effect which aids the intracellular translocation of anti-cancer drugs [63]. Risk of overtreatment could be minimized along with the reduction in dose of therapeutic agent with less laser exposure time. All these can be attained by combination of PDT/PTT. Synergistic effect of PTT/PDT have been seen when GO was loaded with methylene blue [64]. In this system, lesser dose of nano GO was applied, as compared to the particular PTT treatment of nano GO. In addition, the PTT and PDT combinational treatment could be spoil both superficial and deep regions of the tumor, and thus overcome the drawbacks of single treatments [65]. To further progress cancer therapy efficacy, numerous types of theranostic platforms were developed to combine chemotherapy, PTT and PDT simultaneously [66]. Treating cancer with combinational therapy has become an essential trend in cancer therapeutics. Compared to single modality therapy, the combined therapy can reduce the dosage of the drugs and thus decrease the side effects in treatment. More prominently, the combined therapy has the potential to decrease multidrug resistance of tumor cells, thus improving the therapeutic efficacy. The combined therapy may bring a novel opportunity to the next invention of cancer treatment [67].
The theranostic nanoparticles have an ever increasing consideration for image guided therapy in current years because these nanoparticles can follow the pharmacokinetic process, guide the treatment and monitor therapeutic process and outcome. They could be employed to imagine and quantify the performance of drug delivery systems for numerous special purposes such as biodistribution and pharmacokinetics of nanocarriers, metabolic response and drug release process of the nanocarriers. Koukourakis group and Harrington group engaged Technetium and Indium labeled PEGylated liposomes respectively to monitor drug targeting to the sarcomas and breast cancer sites [69]. In the clinical practice, surgical resection is a regular and inevitable procedure for cancer therapy. Theranostics gives a possibility in intraoperative imaging to guide the operation process. During the surgery, physicians could congregate the diagnostic information for precise imaging as well as visualized therapy. In theranostic platform, DOTA-Gd act as a MRI contrast agent for preoperative finding and surgical planning; the Raman molecules visualized the excellent margin of tumor, allowing precise resection for the duration of operation process. The multimodal NP could recognize tumor edge for precise resection of tumor. This approach could be planned for simple intraoperative navigation and real-time imaging [70]. Theranostic technologies commonly utilized for cancer treatment are given in Table 2.
Imaging method | Imaging agent | Therapeutic agent | Function |
---|---|---|---|
Optical Imaging | Cy5.5 | Paclitaxel | Real time tracking of NP location |
FITC-coumarin pair | Doxorubicin | Drug release monitoring | |
Dicyanomethylene-4H-pyran | Camptothecin | Drug release monitoring | |
Cy7, 111In | Cyclophosphamide, etoposide | Real time imaging of apoptosis | |
Cy5.5-BHQ pair | Doxorubicin | Real time imaging of apoptosis | |
Ce6 | Ce6 | Real time tracking of NP location & PDT | |
Ce6-BHQ pair | Ce6 | Drug release monitoring & PDT | |
UCNP (β-NaYF4:Yb3+,Er3+) | Cisplatin prodrug | Imaging of NP location | |
UCNP (NaYF4:Er) | TPGSd | Dual imaging (optical, CT) & reducing multidrug resistance | |
UCNP (NaYF4:Yb/Er) | Ce6, doxorubicin | Imaging of particle location & chemotherapy/PDT | |
MR imaging | Gd | Doxorubicin | Real time monitoring of drug delivery |
SPION | SPION | Detection & hyperthermia treatment of tumor | |
SPION | Doxorubicin | Tumor detection & chemotherapy | |
SPION/FITC | siRNA | MR imaging & gene therapy | |
CT imaging | GNP | Doxorubicin | CT imaging of cancer & chemotherapy |
GNR | GNR | Dual imaging (X-ray/CT) & PTT/radio sensitization | |
PET Imaging | 64Cu | Doxorubicin | Quantitative biodistribution analysis & Chemotherapy |
64Cu | siRNA | Quantitative determination of biodistribution & efficacy of siRNA NPs | |
US imaging | Perfluoropentane | Docetaxel | Triggered drug release & chemotherapy |
CaCO3 | Doxorubicin | Tumor imaging & triggered drug release | |
Perfluorooctyl bromide | Camptothecin | Chemotherapy & ablation therapy | |
Perfluorohexane | CPT11m | Tumor imaging & chemotherapy/ablation Therapy |
Theranostic technologies for cancer treatment [68].
Theranostic approach to management of cancer offers numerous advantages. They are designed to monitor cancer treatment in real time. A wide variety of theranostic nanoplatforms that are based on diverse nanostructures like magnetic nanoparticles, carbon nanotubes, gold nanomaterials, polymeric nanoparticles, or silica nanoparticles showed great potential as cancer theranostics. Nano therapeutic platforms have been successful in integrating image guidance with targeted approach to treat cancer.
Authors declare no conflict of interest related to this manuscript.
PTT | Photothermal therapy |
PDT | Photodynamic therapy |
DOX | Doxorubicin |
NIR | Near infrared |
MRI | Magnetic resonance imaging |
PET | Positron emission tomography |
CT | Computed topography |
UNCPs | Up converting nanoparticles |
GO | Grapheme oxide |
MDR | Multidrug resistance |
MoS2 | Molybdenum disulfide |
ICG | Indocyanine green |
WS2 | Tungsten disulfide |
Ce6 | Chlorine e6 |
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\n\nAll payments shall be due 30 days from the date of the issued invoice. The Corresponding Author or the payer on the Corresponding Author's and Co-Authors' behalf will bear all banking and similar charges incurred.
\n\n3.3 The Corresponding Author shall obtain in writing all consents necessary for the reproduction of any material in which a third-party right exists, including quotations, photographs and illustrations, in all editions of the Chapter worldwide for the full term of the above licenses, and shall provide to IntechOpen upon request the original copies of such consents for inspection (at IntechOpen's option) or photocopies of such consents.
\n\nThe Corresponding Author shall obtain written informed consent for publication from people who might recognize themselves or be identified by others (e.g. from case reports or photographs).
\n\n3.4 The Corresponding Author and any Co-Author shall respect confidentiality rights during and after the termination of this Agreement. The information contained in all correspondence and documents as part of the publishing activity between IntechOpen and the Corresponding Author and any Co-Author are confidential and are intended only for the recipient. The contents may not be disclosed publicly and are not intended for unauthorized use or distribution. Any use, disclosure, copying, or distribution is prohibited and may be unlawful.
\n\n4. CORRESPONDING AUTHOR'S WARRANTY
\n\n4.1 The Corresponding Author represents and warrants that the Chapter does not and will not breach any applicable law or the rights of any third party and, specifically, that the Chapter contains no matter that is defamatory or that infringes any literary or proprietary rights, intellectual property rights, or any rights of privacy. The Corresponding Author warrants and represents that: (i) the Chapter is the original work of themselves and any Co-Author and is not copied wholly or substantially from any other work or material or any other source; (ii) the Chapter has not been formally published in any other peer-reviewed journal or in a book or edited collection, and is not under consideration for any such publication; (iii) they themselves and any Co-Author are qualifying persons under section 154 of the Copyright, Designs and Patents Act 1988; (iv) they themselves and any Co-Author have not assigned and will not during the term of this Publication Agreement purport to assign any of the rights granted to IntechOpen under this Publication Agreement; and (v) the rights granted by this Publication Agreement are free from any security interest, option, mortgage, charge or lien.
\n\nThe Corresponding Author also warrants and represents that: (i) they have the full power to enter into this Publication Agreement on their own behalf and on behalf of each Co-Author; and (ii) they have the necessary rights and/or title in and to the Chapter to grant IntechOpen, on behalf of themselves and any Co-Author, the rights and licenses expressed to be granted in this Publication Agreement. If the Chapter was prepared jointly by the Corresponding Author and any Co-Author, the Corresponding Author warrants and represents that: (i) each Co-Author agrees to the submission, license and publication of the Chapter on the terms of this Publication Agreement; and (ii) they have the authority to enter into this Publication Agreement on behalf of and bind each Co-Author. The Corresponding Author shall: (i) ensure each Co-Author complies with all relevant provisions of this Publication Agreement, including those relating to confidentiality, performance and standards, as if a party to this Publication Agreement; and (ii) remain primarily liable for all acts and/or omissions of each such Co-Author.
\n\nThe Corresponding Author agrees to indemnify and hold IntechOpen harmless against all liabilities, costs, expenses, damages and losses and all reasonable legal costs and expenses suffered or incurred by IntechOpen arising out of or in connection with any breach of the aforementioned representations and warranties. This indemnity shall not cover IntechOpen to the extent that a claim under it results from IntechOpen's negligence or willful misconduct.
\n\n4.2 Nothing in this Publication Agreement shall have the effect of excluding or limiting any liability for death or personal injury caused by negligence or any other liability that cannot be excluded or limited by applicable law.
\n\n5. TERMINATION
\n\n5.1 IntechOpen has a right to terminate this Publication Agreement for quality, program, technical or other reasons with immediate effect, including without limitation (i) if the Corresponding Author or any Co-Author commits a material breach of this Publication Agreement; (ii) if the Corresponding Author or any Co-Author (being an individual) is the subject of a bankruptcy petition, application or order; or (iii) if the Corresponding Author or any Co-Author (being a company) commences negotiations with all or any class of its creditors with a view to rescheduling any of its debts, or makes a proposal for or enters into any compromise or arrangement with any of its creditors.
\n\nIn case of termination, IntechOpen will notify the Corresponding Author, in writing, of the decision.
\n\n6. INTECHOPEN’S DUTIES AND RIGHTS
\n\n6.1 Unless prevented from doing so by events outside its reasonable control, IntechOpen, in its discretion, agrees to publish the Chapter attributing it to the Corresponding Author and any Co-Author.
\n\n6.2 IntechOpen has the right to use the Corresponding Author’s and any Co-Author’s names and likeness in connection with scientific dissemination, retrieval, archiving, web hosting and promotion and marketing of the Chapter and has the right to contact the Corresponding Author and any Co-Author until the Chapter is publicly available on any platform owned and/or operated by IntechOpen.
\n\n6.3 IntechOpen is granted the authority to enforce the rights from this Publication Agreement, on behalf of the Corresponding Author and any Co-Author, against third parties (for example in cases of plagiarism or copyright infringements). In respect of any such infringement or suspected infringement of the copyright in the Chapter, IntechOpen shall have absolute discretion in addressing any such infringement which is likely to affect IntechOpen's rights under this Publication Agreement, including issuing and conducting proceedings against the suspected infringer.
\n\n7. MISCELLANEOUS
\n\n7.1 Further Assurance: The Corresponding Author shall and will ensure that any relevant third party (including any Co-Author) shall, execute and deliver whatever further documents or deeds and perform such acts as IntechOpen reasonably requires from time to time for the purpose of giving IntechOpen the full benefit of the provisions of this Publication Agreement.
\n\n7.2 Third Party Rights: A person who is not a party to this Publication Agreement may not enforce any of its provisions under the Contracts (Rights of Third Parties) Act 1999.
\n\n7.3 Entire Agreement: This Publication Agreement constitutes the entire agreement between the parties in relation to its subject matter. It replaces and extinguishes all prior agreements, draft agreements, arrangements, collateral warranties, collateral contracts, statements, assurances, representations and undertakings of any nature made by or on behalf of the parties, whether oral or written, in relation to that subject matter. Each party acknowledges that in entering into this Publication Agreement it has not relied upon any oral or written statements, collateral or other warranties, assurances, representations or undertakings which were made by or on behalf of the other party in relation to the subject matter of this Publication Agreement at any time before its signature (together "Pre-Contractual Statements"), other than those which are set out in this Publication Agreement. Each party hereby waives all rights and remedies which might otherwise be available to it in relation to such Pre-Contractual Statements. Nothing in this clause shall exclude or restrict the liability of either party arising out of its pre-contract fraudulent misrepresentation or fraudulent concealment.
\n\n7.4 Waiver: No failure or delay by a party to exercise any right or remedy provided under this Publication Agreement or by law shall constitute a waiver of that or any other right or remedy, nor shall it preclude or restrict the further exercise of that or any other right or remedy. No single or partial exercise of such right or remedy shall preclude or restrict the further exercise of that or any other right or remedy.
\n\n7.5 Variation: No variation of this Publication Agreement shall be effective unless it is in writing and signed by the parties (or their duly authorized representatives).
\n\n7.6 Severance: If any provision or part-provision of this Publication Agreement is or becomes invalid, illegal or unenforceable, it shall be deemed modified to the minimum extent necessary to make it valid, legal and enforceable. If such modification is not possible, the relevant provision or part-provision shall be deemed deleted.
\n\nAny modification to or deletion of a provision or part-provision under this clause shall not affect the validity and enforceability of the rest of this Publication Agreement.
\n\n7.7 No partnership: Nothing in this Publication Agreement is intended to, or shall be deemed to, establish or create any partnership or joint venture or the relationship of principal and agent or employer and employee between IntechOpen and the Corresponding Author or any Co-Author, nor authorize any party to make or enter into any commitments for or on behalf of any other party.
\n\n7.8 Governing law: This Publication Agreement and any dispute or claim (including non-contractual disputes or claims) arising out of or in connection with it or its subject matter or formation shall be governed by and construed in accordance with the law of England and Wales. The parties submit to the exclusive jurisdiction of the English courts to settle any dispute or claim arising out of or in connection with this Publication Agreement (including any non-contractual disputes or claims).
\n\nLast updated: 2020-11-27
\n\n\n\n
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